Displaying publications 101 - 120 of 262 in total

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  1. A plethora of human pluripotent stem cells
    Gao L, Thilakavathy K, Nordin N
    Cell Biol Int, 2013 Sep;37(9):875-87.
    PMID: 23619972 DOI: 10.1002/cbin.10120
    At the early stages of mammalian development, a number of developmentally plastic cells appear that possess the ability to give rise to all of the differentiated cell types normally derived from the three primary germ layers - unique character known as pluripotency. To date, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to be truly pluripotent. However, recent studies have revealed a variety of other cells that demonstrate pluripotentiality, including very small embryonic-like stem cells (VSELs), amniotic fluid stem cells (AFSCs), marrow-isolated adult multilineage inducible cells (MIAMI) and multipotent adult precursor cells (MAPCs). This review summarises key features of these six kinds of pluripotent and potentially pluripotent stem cells (ESCs, iPSCs, VSELs, AFSCs, MIAMI and MAPCs) and the evidence for their pluripotency properties.
    Matched MeSH terms: Transcription Factors/genetics; Transcription Factors/metabolism
  2. Fulltext T-cell receptor signaling induces proximal Runx1 transactivation via a calcineurin-NFAT pathway
    Wong WF, Looi CY, Kon S, Movahed E, Funaki T, Chang LY, et al.
    Eur J Immunol, 2014 Mar;44(3):894-904.
    PMID: 24310293 DOI: 10.1002/eji.201343496
    Runx1 transcription factor is a key player in the development and function of T cells. Runx1 transcripts consist of two closely related isoforms (proximal and distal Runx1) whose expressions are regulated by different promoters. Which Runx1 isoform is expressed appears to be tightly regulated. The regulatory mechanism for differential transcription is, however, not fully understood. In this study, we investigated the regulation of the proximal Runx1 promoter in T cells. We showed that proximal Runx1 was expressed at a low level in naïve T cells from C57BL/6 mice, but its expression was remarkably induced upon T-cell activation. In the promoter of proximal Runx1, a highly conserved region was identified which spans from -412 to the transcription start site and harbors a NFAT binding site. In a luciferase reporter assay, this region was found to be responsive to T-cell activation through Lck and calcineurin pathways. Mutagenesis studies and chromatin immunoprecipitation assay indicated that the NFAT site was essential for NFAT binding and transactivation of the proximal Runx1 promoter. Furthermore, TCR signaling-induced expression of proximal Runx1 was blocked by treatment of cells with cyclosporin A. Together, these results demonstrate that the calcineurin-NFAT pathway regulates proximal Runx1 transcription upon TCR stimulation.
    Matched MeSH terms: NFATC Transcription Factors/genetics; NFATC Transcription Factors/metabolism*
  3. Mature B-cell acute lymphoblastic leukaemia associated with a rare MLL-FOXO4 fusion gene
    Lim L, Chen KS, Krishnan S, Gole L, Ariffin H
    Br J Haematol, 2012 Jun;157(6):651.
    PMID: 22429121 DOI: 10.1111/j.1365-2141.2012.09091.x
    Matched MeSH terms: Transcription Factors/genetics*; Transcription Factors/metabolism
  4. Fulltext EgJUB1 and EgERF113 transcription factors as potential master regulators of defense response in Elaeis guineensis against the hemibiotrophic Ganoderma boninense
    Sakeh NM, Abdullah SNA, Bahari MNA, Azzeme AM, Shaharuddin NA, Idris AS
    BMC Plant Biol, 2021 Jan 22;21(1):59.
    PMID: 33482731 DOI: 10.1186/s12870-020-02812-7
    BACKGROUND: Hemibiotrophic pathogen such as the fungal pathogen Ganoderma boninense that is destructive to oil palm, manipulates host defense mechanism by strategically switching from biotrophic to necrotrophic phase. Our previous study revealed two distinguishable expression profiles of oil palm genes that formed the basis in deducing biotrophic phase at early interaction which switched to necrotrophic phase at a later stage of infection.

    RESULTS: The present report is a continuing study from our previous published transcriptomic profiling of oil palm seedlings against G. boninense. We focused on identifying differentially expressed genes (DEGs) encoding transcription factors (TFs) from the same RNA-seq data; resulting in 106 upregulated and 108 downregulated TFs being identified. The DEGs are involved in four established defense-related pathways responsible for cell wall modification, reactive oxygen species (ROS)-mediated signaling, programmed cell death (PCD) and plant innate immunity. We discovered upregulation of JUNGBRUNNEN 1 (EgJUB1) during the fungal biotrophic phase while Ethylene Responsive Factor 113 (EgERF113) demonstrated prominent upregulation when the palm switches to defense against necrotrophic phase. EgJUB1 was shown to have a binding activity to a 19 bp palindromic SNBE1 element, WNNYBTNNNNNNNAMGNHW found in the promoter region of co-expressing EgHSFC-2b. Further in silico analysis of promoter regions revealed co-expression of EgJUB1 with TFs containing SNBE1 element with single nucleotide change at either the 5th or 18th position. Meanwhile, EgERF113 binds to both GCC and DRE/CRT elements promoting plasticity in upregulating the downstream defense-related genes. Both TFs were proven to be nuclear-localized based on subcellular localization experiment using onion epidermal cells.

    CONCLUSION: Our findings demonstrated unprecedented transcriptional reprogramming of specific TFs potentially to enable regulation of a specific set of genes during different infection phases of this hemibiotrophic fungal pathogen. The results propose the intricacy of oil palm defense response in orchestrating EgJUB1 during biotrophic and EgERF113 during the subsequent transition to the necrotrophic phase. Binding of EgJUB1 to SNBE motif instead of NACBS while EgERF113 to GCC-box and DRE/CRT motifs is unconventional and not normally associated with pathogen infection. Identification of these phase-specific oil palm TFs is important in designing strategies to tackle or attenuate the progress of infection.

    Matched MeSH terms: Transcription Factors/genetics; Transcription Factors/metabolism*
  5. Intracellular and exosomal microRNAome profiling of human vascular smooth muscle cells during replicative senescence
    Nguyen DDN, Zain SM, Kamarulzaman MH, Low TY, Chilian WM, Pan Y, et al.
    Am J Physiol Heart Circ Physiol, 2021 10 01;321(4):H770-H783.
    PMID: 34506226 DOI: 10.1152/ajpheart.00058.2021
    Vascular aging is highly associated with cardiovascular morbidity and mortality. Although the senescence of vascular smooth muscle cells (VSMCs) has been well established as a major contributor to vascular aging, intracellular and exosomal microRNA (miRNA) signaling pathways in senescent VSMCs have not been fully elucidated. This study aimed to identify the differential expression of intracellular and exosomal miRNA in human VSMCs (hVSMCs) during replicative senescence. To achieve this aim, intracellular and exosomal miRNAs were isolated from hVSMCs and subsequently subjected to whole genome small RNA next-generation sequencing, bioinformatics analyses, and qPCR validation. Three significant findings were obtained. First, senescent hVSMC-derived exosomes tended to cluster together during replicative senescence and the molecular weight of the exosomal protein tumor susceptibility gene 101 (TSG-101) increased relative to the intracellular TSG-101, suggesting potential posttranslational modifications of exosomal TSG-101. Second, there was a significant decrease in both intracellular and exosomal hsa-miR-155-5p expression [n = 3, false discovery rate (FDR) < 0.05], potentially being a cell type-specific biomarker of hVSMCs during replicative senescence. Importantly, hsa-miR-155-5p was found to associate with cell-cycle arrest and elevated oxidative stress. Lastly, miRNAs from the intracellular pool, that is, hsa-miR-664a-3p, hsa-miR-664a-5p, hsa-miR-664b-3p, hsa-miR-4485-3p, hsa-miR-10527-5p, and hsa-miR-12136, and that from the exosomal pool, that is, hsa-miR-7704, were upregulated in hVSMCs during replicative senescence (n = 3, FDR < 0.05). Interestingly, these novel upregulated miRNAs were not functionally well annotated in hVSMCs to date. In conclusion, hVSMC-specific miRNA expression profiles during replicative senescence potentially provide valuable insights into the signaling pathways leading to vascular aging.NEW & NOTEWORTHY This is the first study on intracellular and exosomal miRNA profiling on human vascular smooth muscle cells during replicative senescence. Specific dysregulated sets of miRNAs were identified from human vascular smooth muscle cells. Hsa-miR-155-5p was significantly downregulated in both intracellular and exosomal hVSMCs, suggesting its crucial role in cellular senescence. Hsa-miR-155-5p might be the mediator in linking cellular senescence to vascular aging and atherosclerosis.
    Matched MeSH terms: Transcription Factors/genetics; Transcription Factors/metabolism
  6. Fulltext Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor
    Lee SH, Wong RR, Chin CY, Lim TY, Eng SA, Kong C, et al.
    Proc Natl Acad Sci U S A, 2013 Sep 10;110(37):15067-72.
    PMID: 23980181 DOI: 10.1073/pnas.1311725110
    Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.
    Matched MeSH terms: GATA Transcription Factors/genetics; GATA Transcription Factors/metabolism*
  7. Fulltext Reduced cardiomyocyte Na+ current in the age-dependent murine Pgc-1β-/- model of ventricular arrhythmia
    Ahmad S, Valli H, Smyth R, Jiang AY, Jeevaratnam K, Matthews HR, et al.
    J Cell Physiol, 2019 Apr;234(4):3921-3932.
    PMID: 30146680 DOI: 10.1002/jcp.27183
    Peroxisome proliferator-activated receptor-γ coactivator-1 deficient (Pgc-1β-/- ) murine hearts model the increased, age-dependent, ventricular arrhythmic risks attributed to clinical conditions associated with mitochondrial energetic dysfunction. These were accompanied by compromised action potential (AP) upstroke rates and impaired conduction velocities potentially producing arrhythmic substrate. We tested a hypothesis implicating compromised Na+ current in these electrophysiological phenotypes by applying loose patch-clamp techniques in intact young and aged, wild-type (WT) and Pgc-1β-/- , ventricular cardiomyocyte preparations for the first time. This allowed conservation of their in vivo extracellular and intracellular conditions. Depolarising steps elicited typical voltage-dependent activating and inactivating inward Na+ currents with peak amplitudes increasing or decreasing with their respective activating or preceding inactivating voltage steps. Two-way analysis of variance associated Pgc-1β-/- genotype with independent reductions in maximum peak ventricular Na+ currents from -36.63 ± 2.14 (n = 20) and -35.43 ± 1.96 (n = 18; young and aged WT, respectively), to -29.06 ± 1.65 (n = 23) and -27.93 ± 1.63 (n = 20; young and aged Pgc-1β-/- , respectively) pA/μm2 (p 
    Matched MeSH terms: Transcription Factors/deficiency*; Transcription Factors/genetics
  8. Fulltext Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk
    Kar SP, Tyrer JP, Li Q, Lawrenson K, Aben KK, Anton-Culver H, et al.
    Cancer Epidemiol Biomarkers Prev, 2015 Oct;24(10):1574-84.
    PMID: 26209509 DOI: 10.1158/1055-9965.EPI-14-1270
    BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.

    METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).

    RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.

    CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.

    IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization.

    Matched MeSH terms: Transcription Factors/biosynthesis; Transcription Factors/genetics
  9. Short-term moderate hypothermia stimulates alkaline phosphatase activity and osteocalcin expression in osteoblasts by upregulating Runx2 and osterix in vitro
    Aisha MD, Nor-Ashikin MN, Sharaniza AB, Nawawi HM, Kapitonova MY, Froemming GR
    Exp Cell Res, 2014 Aug 1;326(1):46-56.
    PMID: 24928274 DOI: 10.1016/j.yexcr.2014.06.003
    Exposure of Normal Human Osteoblast cells (NHOst) to a period of hypothermia may interrupt their cellular functions, lead to changes in bone matrix and disrupt the balance between bone formation and resorption, resulting in bone loss or delayed fracture healing. To investigate this possibility, we exposed NHOst cells to moderate (35 °C) and severe (27 °C) hypothermia for 1, 12, 24 and 72 h. The effects of hypothermia with respect to cell cytoskeleton organization, metabolic activity and the expression of cold shock chaperone proteins, osteoblast transcription factors and functional markers, were examined. Our findings showed that prolonged moderate hypothermia retained the polymerization of the cytoskeletal components. NHOst cell metabolism was affected differently according to hypothermia severity. The osteoblast transcription factors Runx2 and osterix were necessary for the transcription and translation of bone matrix proteins, where alkaline phosphatase (Alp) activity and osteocalcin (OCN) bone protein were over expressed under hypothermic conditions. Consequently, bone mineralization was stimulated after exposure to moderate hypothermia for 1 week, indicating bone function was not impaired. The cold shock chaperone protein Rbm3 was significantly upregulated (p<0.001) during the cellular stress adaption under hypothermic conditions. We suggest that Rbm3 has a dual function: one as a chaperone protein that stabilizes mRNA transcripts and a second one in enhancing the transcription of Alp and Ocn genes. Our studies demonstrated that hypothermia permitted the in vitro maturation of NHOst cells probably through an osterix-dependent pathway. For that reason, we suggest that moderate hypothermia can be clinically applied to counteract heat production at the fracture site that delays fracture healing.
    Matched MeSH terms: Transcription Factors/genetics; Transcription Factors/metabolism*
  10. Fulltext Cloning and characterization of short-chain N-acyl homoserine lactone-producing Enterobacter asburiae strain L1 from lettuce leaves
    Lau YY, How KY, Yin WF, Chan KG
    Microbiologyopen, 2018 Dec;7(6):e00610.
    PMID: 29982994 DOI: 10.1002/mbo3.610
    In gram-negative bacteria, bacterial communication or quorum sensing (QS) is achieved using common signaling molecules known as N-acyl homoserine lactones (AHL). We have previously reported the genome of AHL-producing bacterium, Enterobacter asburiae strain L1. In silico analysis of the strain L1 genome revealed the presence of a pair of luxI/R genes responsible for AHL-type QS, designated as easIR. In this work, the 639 bp luxI homolog, encoding 212 amino acids, have been cloned and overexpressed in Escherichia coli BL21 (DE3)pLysS. The purified protein (~25 kDa) shares high similarity to several members of the LuxI family among different E asburiae strains. Our findings showed that the heterologously expressed EasI protein has activated violacein production by AHL biosensor Chromobacterium violaceum CV026 as the wild-type E. asburiae. The mass spectrometry analysis showed the production of N-butanoyl homoserine lactone and N-hexanoyl homoserine lactone from induced E. coli harboring the recombinant EasI, suggesting that EasI is a functional AHL synthase. E. asburiae strain L1 was also shown to possess biofilm-forming characteristic activity using crystal violet binding assay. This is the first report on cloning and characterization of the luxI homolog from E. asburiae.
    Matched MeSH terms: Transcription Factors/genetics*; Transcription Factors/metabolism
  11. Targeting Yes-Associated Protein (YAP) in Breast Cancer: In Silico Molecular Dynamics, Luminescence-Based In Vitro, and In Vivo Validation of Rauvolfia tetraphylla-Derived Inhibitors
    Balavaishnavi B, Kamaraj M, Nithya TG, Sathish S, Madhavan T, Mahajan M, et al.
    Luminescence, 2024 Dec;39(12):e70051.
    PMID: 39681523 DOI: 10.1002/bio.70051
    The study aims to elucidate the pharmacological mechanism of Rauvolfia tetraphylla against breast cancer through a comprehensive, multi-faceted approach. This includes molecular docking, molecular dynamics, and experimental validation. Initial screening via ADME analysis and network pharmacology identified key compounds and potential targets. Protein-protein interaction (PPI) network analysis pinpointed Yes-associated protein-1 (YAP) as a crucial target. Molecular docking revealed that three compounds-ajmaline, reserpine, and serpentine-exhibited strong binding affinities with YAP, with scores of -6.5 to -6.7 kcal/mol. Molecular dynamics simulations were conducted to assess the stability of these interactions further. Experimental validation showed R. tetraphylla inhibited breast cancer cell proliferation, with an IC50 of 348.69 μg/mL, while demonstrating cytoprotective effects on Vero cells (IC50: 1056.23 μg/mL). Migration assays indicated an 88.5% reduction in cell migration, and increased ROS levels signaled elevated stress in cancer cells. Apoptosis was confirmed by AO/EtBr staining. In vivo validation in a DMBA-induced mouse model confirmed significant tumor growth inhibition, supported by changes in YAP expression and histopathological analysis. These findings highlight R. tetraphylla as a promising therapeutic candidate against breast cancer, offering insights into its mechanisms and potential for future drug development and clinical applications.
    Matched MeSH terms: Transcription Factors/antagonists & inhibitors; Transcription Factors/metabolism
  12. The RUNX complex: reaching beyond haematopoiesis into immunity
    Voon DC, Hor YT, Ito Y
    Immunology, 2015 Dec;146(4):523-36.
    PMID: 26399680 DOI: 10.1111/imm.12535
    Among their diverse roles as transcriptional regulators during development and cell fate specification, the RUNX transcription factors are best known for the parts they play in haematopoiesis. RUNX proteins are expressed throughout all haematopoietic lineages, being necessary for the emergence of the first haematopoietic stem cells to their terminal differentiation. Although much progress has been made since their discoveries almost two decades ago, current appreciation of RUNX in haematopoiesis is largely grounded in their lineage-specifying roles. In contrast, the importance of RUNX to immunity has been mostly obscured for historic, technical and conceptual reasons. However, this paradigm is likely to shift over time, as a primary purpose of haematopoiesis is to resource the immune system. Furthermore, recent evidence suggests a role for RUNX in the innate immunity of non-haematopoietic cells. This review takes a haematopoiesis-centric approach to collate what is known of RUNX's contribution to the overall mammalian immune system and discuss their growing prominence in areas such as autoimmunity, inflammatory diseases and mucosal immunity.
    Matched MeSH terms: Transcription Factors
  13. Fulltext Effects of glucose, ethanol and acetic acid on regulation of ADH2 gene from Lachancea fermentati
    Yaacob N, Mohamad Ali MS, Salleh AB, Abdul Rahman NA
    PeerJ, 2016;4:e1751.
    PMID: 26989608 DOI: 10.7717/peerj.1751
    Background. Not all yeast alcohol dehydrogenase 2 (ADH2) are repressed by glucose, as reported in Saccharomyces cerevisiae. Pichia stipitis ADH2 is regulated by oxygen instead of glucose, whereas Kluyveromyces marxianus ADH2 is regulated by neither glucose nor ethanol. For this reason, ADH2 regulation of yeasts may be species dependent, leading to a different type of expression and fermentation efficiency. Lachancea fermentati is a highly efficient ethanol producer, fast-growing cells and adapted to fermentation-related stresses such as ethanol and organic acid, but the metabolic information regarding the regulation of glucose and ethanol production is still lacking. Methods. Our investigation started with the stimulation of ADH2 activity from S. cerevisiae and L. fermentati by glucose and ethanol induction in a glucose-repressed medium. The study also embarked on the retrospective analysis of ADH2 genomic and protein level through direct sequencing and sites identification. Based on the sequence generated, we demonstrated ADH2 gene expression highlighting the conserved NAD(P)-binding domain in the context of glucose fermentation and ethanol production. Results. An increase of ADH2 activity was observed in starved L. fermentati (LfeADH2) and S. cerevisiae (SceADH2) in response to 2% (w/v) glucose induction. These suggest that in the presence of glucose, ADH2 activity was activated instead of being repressed. An induction of 0.5% (v/v) ethanol also increased LfeADH2 activity, promoting ethanol resistance, whereas accumulating acetic acid at a later stage of fermentation stimulated ADH2 activity and enhanced glucose consumption rates. The lack in upper stream activating sequence (UAS) and TATA elements hindered the possibility of Adr1 binding to LfeADH2. Transcription factors such as SP1 and RAP1 observed in LfeADH2 sequence have been implicated in the regulation of many genes including ADH2. In glucose fermentation, L. fermentati exhibited a bell-shaped ADH2 expression, showing the highest expression when glucose was depleted and ethanol-acetic acid was increased. Meanwhile, S. cerevisiae showed a constitutive ADH2 expression throughout the fermentation process. Discussion. ADH2 expression in L. fermentati may be subjected to changes in the presence of non-fermentative carbon source. The nucleotide sequence showed that ADH2 transcription could be influenced by other transcription genes of glycolysis oriented due to the lack of specific activation sites for Adr1. Our study suggests that if Adr1 is not capable of promoting LfeADH2 activation, the transcription can be controlled by Rap1 and Sp1 due to their inherent roles. Therefore in future, it is interesting to observe ADH2 gene being highly regulated by these potential transcription factors and functioned as a promoter for yeast under high volume of ethanol and organic acids.
    Matched MeSH terms: Transcription Factors
  14. Fulltext Transcription Factor CREB3L1 Regulates Endoplasmic Reticulum Stress Response Genes in the Osmotically Challenged Rat Hypothalamus
    Greenwood M, Greenwood MP, Paton JF, Murphy D
    PLoS One, 2015;10(4):e0124956.
    PMID: 25915053 DOI: 10.1371/journal.pone.0124956
    Arginine vasopressin (AVP) is synthesised in magnocellular neurons (MCNs) of supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. In response to the hyperosmotic stressors of dehydration (complete fluid deprivation, DH) or salt loading (drinking 2% salt solution, SL), AVP synthesis increases in MCNs, which over-burdens the protein folding machinery in the endoplasmic reticulum (ER). ER stress and the unfolded protein response (UPR) are signaling pathways that improve ER function in response to the accumulation of misfold/unfold protein. We asked whether an ER stress response was activated in the SON and PVN of DH and SL rats. We observed increased mRNA expression for the immunoglobulin heavy chain binding protein (BiP), activating transcription factor 4 (Atf4), C/EBP-homologous protein (Chop), and cAMP responsive element binding protein 3 like 1 (Creb3l1) in both SON and PVN of DH and SL rats. Although we found no changes in the splicing pattern of X box-binding protein 1 (Xbp1), an increase in the level of the unspliced form of Xbp1 (Xbp1U) was observed in DH and SL rats. CREB3L1, a novel ER stress inducer, has been shown to be activated by ER stress to regulate the expression of target genes. We have previously shown that CREB3L1 is a transcriptional regulator of the AVP gene; however, a role for CREB3L1 in the response to ER stress has yet to be investigated in MCNs. Here, we used lentiviral vectors to introduce a dominant negative form of CREB3L1 (CREB3L1DN) in the rat SON. Expression of CREB3L1DN in the SON decreased Chop and Xbp1U mRNA levels, but not BiP and Atf4 transcript expression. CREB3L1 is thus implicated as a transcriptional mediator of the ER stress response in the osmotically stimulated SON.
    Matched MeSH terms: Transcription Factors/genetics; Transcription Factors/metabolism; Regulatory Factor X Transcription Factors
  15. Regulation of gene expression mediating indeterminate muscle growth in teleosts
    Ahammad AK, Asaduzzaman M, Asakawa S, Watabe S, Kinoshita S
    Mech. Dev., 2015 Aug;137:53-65.
    PMID: 25842264 DOI: 10.1016/j.mod.2015.02.006
    Teleosts are unique among vertebrates due to their indeterminate muscle growth, i.e., continued production of neonatal muscle fibers until death. However, the molecular mechanism(s) underlying this property is unknown. Here, we focused on the torafugu (Takifugu rubripes) myosin heavy chain gene, MYHM2528-1, which is specifically expressed in neonatal muscle fibers produced by indeterminate muscle growth. We examined the flanking region of MYHM2528-1 through an in vivo reporter assay using zebrafish (Danio rerio) and identified a 2100 bp 5'-flanking sequence that contained sufficient promoter activity to allow specific gene expression. The effects of enhanced promoter activity were observed at the outer region of the fast muscle and the dorsal edge of slow muscle in zebrafish larvae. At the juvenile stage, the promoter was specifically activated in small diameter muscle fibers scattered throughout fast muscle and in slow muscle near the septum separating slow and fast muscles. This spatio-temporal promoter activity overlapped with known myogenic zones involved in teleost indeterminate muscle growth. A deletion mutant analysis revealed that the -2100 to -600 bp 5'flanking sequence of MYHM2528-1 is essential for promoter activity. This region contains putative binding sites for several representative myogenesis-related transcription factors and nuclear factor of activated T-cell (NFAT), a transcription activator involved in regeneration of mammalian adult skeletal muscle. A significant reduction in the promoter activity of the MYHM2528-1 deletion constructs was observed in accordance with a reduction in the number of these binding sites, suggesting the involvement of specific transcription factors in indeterminate muscle growth.
    Matched MeSH terms: Transcription Factors/genetics; NFATC Transcription Factors/genetics
  16. Current progress in production of flavonoids using systems and synthetic biology platforms
    Ku Nurul Aqmar Ku Bahaudin, Ahmad Bazli Ramzi, Syarul Nataqain Baharum, Suriana Sabri, Adam Leow Thean Chor, Tewin Tencomnao
    Sains Malaysiana, 2018;47:3077-3084.
    Flavonoid is an industrially-important compound due to its high pharmaceutical and cosmeceutical values. However,
    conventional methods in extracting and synthesizing flavonoids are costly, laborious and not sustainable due to small
    amount of natural flavonoids, large amounts of chemicals and space used. Biotechnological production of flavonoids
    represents a viable and sustainable route especially through the use of metabolic engineering strategies in microbial
    production hosts. In this review, we will highlight recent strategies for the improving the production of flavonoids
    using synthetic biology approaches in particular the innovative strategies of genetically-encoded biosensors for in
    vivo metabolite analysis and high-throughput screening methods using fluorescence-activated cell sorting (FACS).
    Implementation of transcription factor based-biosensor for microbial flavonoid production and integration of systems
    and synthetic biology approaches for natural product development will also be discussed.
    Matched MeSH terms: Transcription Factors
  17. Fulltext Recommendations by the Asian Pacific society of nephrology (APSN) on the appropriate use of HIF-PH inhibitors
    Yap DYH, McMahon LP, Hao CM, Hu N, Okada H, Suzuki Y, et al.
    Nephrology (Carlton), 2021 Feb;26(2):105-118.
    PMID: 33222343 DOI: 10.1111/nep.13835
    Renal anaemia is a common and important complication in patients with chronic kidney disease (CKD). The current standard-of-care treatment for renal anaemia in CKD patients involves ensuring adequate iron stores and administration of erythropoietin stimulating agents (ESA). Hypoxia inducible factor (HIF) is a key transcription factor primarily involved in the cellular regulation and efficiency of oxygen delivery. Manipulation of the HIF pathway by the use of HIF-prolyl hydroxylase inhibitors (HIF-PHI) has emerged as a novel approach for renal anaemia management. Despite it being approved for clinical use in various Asia-Pacific countries, its novelty mandates the need for nephrologists and clinicians generally in the region to well understand potential benefits and harms when prescribing this class of drug. The Asian Pacific society of nephrology HIF-PHI Recommendation Committee, formed by a panel of 11 nephrologists from the Asia-Pacific region who have clinical experience or have been investigators in HIF-PHI studies, reviewed and deliberated on the clinical and preclinical data concerning HIF-PHI. This recommendation summarizes the consensus views of the committee regarding the use of HIF-PHI, taking into account both available data and expert opinion in areas where evidence remains scarce.
    Matched MeSH terms: Transcription Factors
  18. Fulltext Expression of Repressor Element 1 Silencing Transcription Factor (REST) in Serotonin Neurons in the Adult Male Nile Tilapia (Oreochromis niloticus)
    Soga T, Nakajima S, Parhar IS
    Front Neuroanat, 2020;14:599540.
    PMID: 33776659 DOI: 10.3389/fnana.2020.599540
    Repressor element-1 silencing transcription factor (REST) is highly expressed in the dorsal raphe where serotonin (5-hydroxytryptamine, 5-HT) neurons are located. REST works as a transcription factor for the 5-HT receptor and tryptophan hydroxylase two-gene expression. We hypothesized that REST is co-expressed in 5-HT neurons, which, if demonstrated, would be useful to understand the mechanism of 5-HT dysfunction-related disorders such as negative emotions and depression. Therefore, the present study was designed to examine the expression of the REST gene in the brain (forebrain, midbrain, and hindbrain) of adult male Nile tilapia (Oreochromis niloticus) using rt-PCR. Besides, using immunocytochemistry, co-localization of the REST gene was examined in 5-HT neurons and with neuronal-/glial-cell markers. We found a high expression of the REST gene in the midbrain region of the dorsal raphe, an area of 5-HT neurons. Double-label immunocytochemistry showed neuron-specific expression of REST co-localized in 5-HT neurons in the dorsal and ventral parts of the periventricular pretectal nucleus, paraventricular organ, and dorsal and medial raphe nucleus. Since midbrain 5-HT neurons express REST, we speculate that REST may control 5-HT neuronal activity related to negative emotions, including depression.
    Matched MeSH terms: Transcription Factors
  19. Differential transcriptional expression of PPARalpha, PPARgamma1, and PPARgamma2 in the peritoneal macrophages and T-cell subsets of non-obese diabetic mice
    Yaacob NS, Kaderi MA, Norazmi MN
    J Clin Immunol, 2009 Sep;29(5):595-602.
    PMID: 19472040 DOI: 10.1007/s10875-009-9300-1
    BACKGROUND: The peroxisome proliferator-activated receptors (PPARs) have been implicated in immune regulation. We determined the transcriptional expression of the three isoforms, PPARalpha, PPARgamma1, and PPARgamma2 in the peritoneal macrophages, CD4- and CD8-positive lymphocytes in non-obese diabetic (NOD) mice at 5 and 10 weeks of age as well as at diabetic stage.

    RESULTS: Compared to the non-obese diabetic resistant (NOR) mice, the peritoneal macrophages of NOD mice expressed increased levels of PPARalpha but reduced levels of PPARgamma2, while PPARgamma1 expression was unchanged in all age groups. CD4-positive lymphocytes expressed low levels of PPARalpha in diabetic NOD mice and greatly reduced expression of PPARgamma2 in all age groups. Unlike peritoneal macrophages and CD4-positive cells, the CD8-positive cells expressed low levels of PPARgamma1 in diabetic NOD mice but no difference in PPARalpha and PPARgamma2 expression was observed compared to NOR mice.

    CONCLUSION: The current findings may suggest an important regulatory role of PPARs in the pathogenesis of autoimmune diabetes.

    Matched MeSH terms: Transcription Factors/genetics; Transcription Factors/immunology; Transcription Factors/metabolism*
  20. [Molecular regulatory mechanisms of hypoxia-inducible factor and interventional effect of Chinese herbal medicine]
    Bu-Hui L, Mei-Zi W, Wei S, Yi-Gang W, Wei WU, Qi-Jun F, et al.
    Zhongguo Zhong Yao Za Zhi, 2020 Oct;45(20):4805-4811.
    PMID: 33350250 DOI: 10.19540/j.cnki.cjcmm.20200630.602
    Hypoxia-inducible factors(HIFs)are the key transcription factors that sense and regulate cellular oxygen concentration in vivo. HIF-1 is composed of 2 subunits,α and β,in which,the molecular regulatory mechanism of HIF-1α involves the main processes of its degradation and activation. The degradation of HIF-1α is regulated by oxygen-dependent pathways,including "von hippel-lindau protein(pVHL)-dependent pathway" and "pVHL-independent pathway". The activation of HIF-1α is regulated by oxygen-independent pathways,including mammalian target of rapamycin(mTOR)/eukaryotic initiation factor 4 E-binding protein 1(4 EBP1)/HIF-1α pathway,phosphatidylinositol 3-kinase(PI3 K)/proteirrserinc-threonine kinases(Akt)/HIF-1α pathway and silent information regulator1(Sirt1)/HIF-1α pathway. In recent years,based on the molecular regulatory mechanism of HIFs,Roxadustat,a new drug for the treatment of renal anemia has been developed. Besides, some macromolecular substances with similar pharmacological effect to HIFs have been found in the extracts from Chinese herbal medicine(CHM),such as emodin,notoginseng triterpenes,honokiol and clematichinenoside. These natural macromolecular substances play the regulatory roles in inflammatory response,epigenetic modification and auto-phagy. It is worth noting that,for common hypoxic-related diseases including diabetic kidney disease,HIFs-mediated "pyroptosis" may be a new target of CHMs for clearing dampness and heat and its representative classical prescriptions(Ermiao Pills)in treating inflammatory injury in cells and tissues.
    Matched MeSH terms: Transcription Factors
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