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Frontiers in Immunology 2023The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are...
The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren's syndrome and Lupus in humans and, germline deletion of the gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for polymorphisms associated with B cell dominated autoimmune diseases in humans.
Topics: Humans; Mice; Animals; Transcription Factors; Chromatin; Protein Binding; Sjogren's Syndrome; Transcription Factors, TFIII; Transcription Factors, TFII
PubMed: 36756127
DOI: 10.3389/fimmu.2023.1067459 -
Nature Oct 2018The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by...
The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin. Here we show that the activation of p300 directly depends on the activation and oligomerization status of transcription factor ligands. Using two model transcription factors, IRF3 and STAT1, we demonstrate that transcription factor dimerization enables the trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop, resulting in p300 activation. We describe a crystal structure of p300 in which the autoinhibitory loop invades the active site of a neighbouring HAT domain, revealing a snapshot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves the rearrangement of an autoinhibitory RING domain. Our data explain how cellular signalling and the activation and dimerization of transcription factors control the activation of p300, and therefore explain why gene transcription is associated with chromatin acetylation.
Topics: Acetylation; Catalytic Domain; Chromatin; Crystallography, X-Ray; Enzyme Activation; Humans; Interferon Regulatory Factor-3; Ligands; Lysine; Models, Molecular; Protein Domains; Protein Multimerization; STAT1 Transcription Factor; Transcription Factors; Transcription, Genetic; p300-CBP Transcription Factors
PubMed: 30323286
DOI: 10.1038/s41586-018-0621-1 -
BioFactors (Oxford, England) 2010In recent years, much progress has been made in understanding the factors that regulate the gene expression program that underlies the induction, proliferation,... (Review)
Review
In recent years, much progress has been made in understanding the factors that regulate the gene expression program that underlies the induction, proliferation, differentiation, and maturation of osteoblasts. A large and growing number of transcription factors make important contributions to the precise control of osteoblast formation and function. It has become increasingly clear that these diverse transcription factors and the signals that regulate their activity cannot be viewed as discrete, separate signaling pathways. Rather, they form a highly interconnected, cooperative network that permits gene expression to be closely regulated. There has also been a substantial increase in our understanding of the mechanistic control of gene expression by cofactors such as acetyltransferases and histone deacetylases. The purpose of this review is to highlight recent progress in understanding the major transcription factors and epigenetic coregulators, including histone deacetylases and microRNAs, involved in osteoblastogenesis and the mechanisms that determine their functions as regulators of gene expression.
Topics: Activating Transcription Factor 4; Animals; Calcineurin; Core Binding Factor Alpha 1 Subunit; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Histone Deacetylases; Humans; Lymphoid Enhancer-Binding Factor 1; Mice; MicroRNAs; NFATC Transcription Factors; Osteoblasts; Smad Proteins; Sp7 Transcription Factor; T Cell Transcription Factor 1; Transcription Factor AP-1; Transcription Factors; Twist-Related Protein 1; Zinc Fingers
PubMed: 20087883
DOI: 10.1002/biof.72 -
BioEssays : News and Reviews in... Apr 2000RNA chain elongation by RNA polymerase II (pol II) is a complex and regulated process which is coordinated with capping, splicing, and polyadenylation of the primary... (Review)
Review
RNA chain elongation by RNA polymerase II (pol II) is a complex and regulated process which is coordinated with capping, splicing, and polyadenylation of the primary transcript. Numerous elongation factors that enable pol II to transcribe faster and/or more efficiently have been purified. SII is one such factor. It helps pol II bypass specific blocks to elongation that are encountered during transcript elongation. SII was first identified biochemically on the basis of its ability to enable pol II to synthesize long transcripts. ((1)) Both the high resolution structure of SII and the details of its novel mechanism of action have been refined through mutagenesis and sophisticated in vitro assays. SII engages transcribing pol II and assists it in bypassing blocks to elongation by stimulating a cryptic, nascent RNA cleavage activity intrinsic to RNA polymerase. The nuclease activity can also result in removal of misincorporated bases from RNA. Molecular genetic experiments in yeast suggest that SII is generally involved in mRNA synthesis in vivo and that it is one type of a growing collection of elongation factors that regulate pol II. In vertebrates, a family of related SII genes has been identified; some of its members are expressed in a tissue-specific manner. The principal challenge now is to understand the isoform-specific functional differences and the biology of regulation exerted by the SII family of proteins on target genes, particularly in multicellular organisms.
Topics: Animals; Humans; Protein Conformation; Protein Isoforms; Transcription Factors; Transcription Factors, General; Transcriptional Elongation Factors
PubMed: 10723030
DOI: 10.1002/(SICI)1521-1878(200004)22:4<327::AID-BIES3>3.0.CO;2-4 -
Biochimica Et Biophysica Acta 2010O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of nuclear and cytoplasmic proteins is important for many cellular processes, and the number of proteins that... (Review)
Review
O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of nuclear and cytoplasmic proteins is important for many cellular processes, and the number of proteins that contain this modification is steadily increasing. This modification is dynamic and reversible, and in some cases competes for phosphorylation of the same residues. O-GlcNAc modification of proteins is regulated by cell cycle, nutrient metabolism, and other extracellular signals. Compared to protein phosphorylation, which is mediated by a large number of kinases, O-GlcNAc modification is catalyzed only by one enzyme called O-linked N-acetylglucosaminyl transferase or OGT. Removal of O-GlcNAc from proteins is catalyzed by the enzyme beta-N-acetylglucosaminidase (O-GlcNAcase or OGA). Altered O-linked GlcNAc modification levels contribute to the establishment of many diseases, such as cancer, diabetes, cardiovascular disease, and neurodegeneration. Many transcription factors have been shown to be modified by O-linked GlcNAc modification, which can influence their transcriptional activity, DNA binding, localization, stability, and interaction with other co-factors. This review focuses on modulation of transcription factor function by O-linked GlcNAc modification.
Topics: Acetylglucosamine; Active Transport, Cell Nucleus; Animals; Cyclic AMP Response Element-Binding Protein; Glycosylation; Humans; Models, Biological; N-Acetylglucosaminyltransferases; NF-kappa B; Protein Interaction Domains and Motifs; Protein Processing, Post-Translational; Protein Stability; Receptors, Estrogen; STAT5 Transcription Factor; Trans-Activators; Transcription Factors; Tumor Suppressor Protein p53; YY1 Transcription Factor; beta-N-Acetylhexosaminidases
PubMed: 20202486
DOI: 10.1016/j.bbagrm.2010.02.005 -
The Journal of Experimental Medicine Nov 2010A relatively small cadre of lineage-restricted transcription factors largely orchestrates erythropoiesis, but how these nuclear factors interact to regulate this complex... (Review)
Review
A relatively small cadre of lineage-restricted transcription factors largely orchestrates erythropoiesis, but how these nuclear factors interact to regulate this complex biology is still largely unknown. However, recent technological advances, such as chromatin immunoprecipitation (ChIP) paired with massively parallel sequencing (ChIP-seq), gene expression profiling, and comprehensive bioinformatic analyses, offer new insights into the intricacies of red cell molecular circuits.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Chromatin Immunoprecipitation; Computational Biology; Erythropoiesis; GATA1 Transcription Factor; Gene Expression Profiling; Humans; Kruppel-Like Transcription Factors; Proto-Oncogene Proteins; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription Factors
PubMed: 21098097
DOI: 10.1084/jem.20102260 -
FEBS Letters May 2006Engrailed is a homeodomain-containing transcription factor with numerous, overlapping roles in neural development. Its multifunctional nature depends upon an extremely... (Review)
Review
Engrailed is a homeodomain-containing transcription factor with numerous, overlapping roles in neural development. Its multifunctional nature depends upon an extremely diverse group of molecular functions including the ability to regulate both transcription and translation, and to be released from and internalized by cells. Recent findings have shown how some of these functions relate to specific roles in development and disease.
Topics: Aging; Animals; Cell Shape; Gene Expression Regulation, Developmental; Neurons; Protein Binding; Transcription Factors
PubMed: 16674951
DOI: 10.1016/j.febslet.2006.04.053 -
BioMed Research International 2015Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5-20 bp...
Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5-20 bp long) specifically bound by one or more transcription factors. The identification of transcription factor binding sites and prediction of their function continue to be challenging problems in computational biology. In this study, by integrating the DNase I hypersensitive sites with known position weight matrices in the TRANSFAC database, the transcription factor binding sites in gene regulatory region are identified. Based on the global gene expression patterns in cervical cancer HeLaS3 cell and HelaS3-ifnα4h cell (interferon treatment on HeLaS3 cell for 4 hours), we present a model-based computational approach to predict a set of transcription factors that potentially cause such differential gene expression. Significantly, 6 out 10 predicted functional factors, including IRF, IRF-2, IRF-9, IRF-1 and IRF-3, ICSBP, belong to interferon regulatory factor family and upregulate the gene expression levels responding to the interferon treatment. Another factor, ISGF-3, is also a transcriptional activator induced by interferon alpha. Using the different transcription factor binding sites selected criteria, the prediction result of our model is consistent. Our model demonstrated the potential to computationally identify the functional transcription factors in gene regulation.
Topics: Binding Sites; Deoxyribonuclease I; Gene Expression Regulation; HeLa Cells; Humans; Transcription Factors
PubMed: 26425553
DOI: 10.1155/2015/757530 -
Experimental & Molecular Medicine Jun 2021Ectopic expression of Oct4, Sox2, Klf4 and c-Myc can reprogram somatic cells into induced pluripotent stem cells (iPSCs). Attempts to identify genes or chemicals that... (Review)
Review
Ectopic expression of Oct4, Sox2, Klf4 and c-Myc can reprogram somatic cells into induced pluripotent stem cells (iPSCs). Attempts to identify genes or chemicals that can functionally replace each of these four reprogramming factors have revealed that exogenous Oct4 is not necessary for reprogramming under certain conditions or in the presence of alternative factors that can regulate endogenous Oct4 expression. For example, polycistronic expression of Sox2, Klf4 and c-Myc can elicit reprogramming by activating endogenous Oct4 expression indirectly. Experiments in which the reprogramming competence of all other Oct family members tested and also in different species have led to the decisive conclusion that Oct proteins display different reprogramming competences and species-dependent reprogramming activity despite their profound sequence conservation. We discuss the roles of the structural components of Oct proteins in reprogramming and how donor cell epigenomes endow Oct proteins with different reprogramming competences.
Topics: Cell Differentiation; Cells, Cultured; Cellular Reprogramming; Fibroblasts; Induced Pluripotent Stem Cells; Kruppel-Like Transcription Factors; Octamer Transcription Factor-3; SOXB1 Transcription Factors; Transcription Factors
PubMed: 34117345
DOI: 10.1038/s12276-021-00637-4 -
Gene Expression 2010X-box binding protein 1 (XBP1) is a unique basic region leucine zipper (bZIP) transcription factor whose active form is generated by a nonconventional splicing reaction... (Review)
Review
X-box binding protein 1 (XBP1) is a unique basic region leucine zipper (bZIP) transcription factor whose active form is generated by a nonconventional splicing reaction upon disruption of homeostasis in the endoplasmic reticulum (ER) and activation of the unfolded protein response (UPR). XBP1, first identified as a key regulator of major histocompatibility complex (MHC) class II gene expression in B cells, represents the most conserved signaling component of UPR and is critical for cell fate determination in response to ER stress. Here we review recent advances in our understanding of this multifaceted transcription factor in health and diseases.
Topics: Amino Acid Sequence; Animals; DNA-Binding Proteins; Disease; Health; Humans; Immunity; Molecular Sequence Data; Regulatory Factor X Transcription Factors; Transcription Factors; Unfolded Protein Response; X-Box Binding Protein 1
PubMed: 21061914
DOI: 10.3727/105221610x12819686555051