scholarly journals Nucleosomes and regulation of gene expression. Structure of the HIV-1 5'LTR.

1998 ◽  
Vol 45 (1) ◽  
pp. 209-219 ◽  
Author(s):  
P Widłak ◽  
W T Garrard
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Chromatin Remodeling ◽  
Binding Sites ◽  
Regulation Of Gene Expression ◽  
Dnase I ◽  
Chromatin Assembly ◽  
Hypersensitive Sites ◽  
Hiv 1

Packaging of DNA into chromatin adds complexity to the problem of regulation of gene expression. Nucleosomes affect the accessibility of transcription factors to occupy their binding sites in chromatin of eukaryotic cells. The disruption of nucleosome structure within the enhancer/promoter region of the integrated HIV-1 proviral genome is an instructive example of a chromatin remodeling process during transcriptional activation. To investigate the mechanism responsible for generating nuclease hypersensitive sites that exist in vivo in the promoter/enhancer region of the 5'LTR (long terminal repeat) of integrated HIV-1 we have utilized an in vitro chromatin assembly system with Xenopus oocyte extracts. Chromatin assembly in the presence of Sp1 and NFkappaB transcription factors induces DNase I hypersensitive sites on either side of their binding sites and positions the adjacent nucleosomes. This structure can also be formed in a factor-induced, ATP-dependent chromatin remodeling process and closely resembles the in vivo chromatin structure. The DNase I hypersensitive sites that form within the HIV LTR are probably histone-free and remain after removal of transcription factors.

scholarly journals Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets

2016 ◽  
Vol 113 (13) ◽  
pp. E1835-E1843 ◽  
Author(s):  
Mina Fazlollahi ◽  
Ivor Muroff ◽  
Eunjee Lee ◽  
Helen C. Causton ◽  
Harmen J. Bussemaker
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Nonsynonymous Mutation ◽  
Gene Regulatory ◽  
Genetic Modulators

Regulation of gene expression by transcription factors (TFs) is highly dependent on genetic background and interactions with cofactors. Identifying specific context factors is a major challenge that requires new approaches. Here we show that exploiting natural variation is a potent strategy for probing functional interactions within gene regulatory networks. We developed an algorithm to identify genetic polymorphisms that modulate the regulatory connectivity between specific transcription factors and their target genes in vivo. As a proof of principle, we mapped connectivity quantitative trait loci (cQTLs) using parallel genotype and gene expression data for segregants from a cross between two strains of the yeast Saccharomyces cerevisiae. We identified a nonsynonymous mutation in the DIG2 gene as a cQTL for the transcription factor Ste12p and confirmed this prediction empirically. We also identified three polymorphisms in TAF13 as putative modulators of regulation by Gcn4p. Our method has potential for revealing how genetic differences among individuals influence gene regulatory networks in any organism for which gene expression and genotype data are available along with information on binding preferences for transcription factors.

Lineage-Specific Transcriptional Regulation of GATA1 Is Dependent on Lineage-Specific Utilisation of Multiple Cis-Elements and Haematopoietic Transcription Factors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1610-1610
Author(s):  
Paresh Vyas ◽  
Boris Guyot ◽  
Veronica Valverde-Garduno ◽  
Eduardo Anguita ◽  
Isla Hamlett ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Dnase I ◽  
Red Cells ◽  
Erythroid Cells ◽  
Cis Elements ◽  
Dnase I Hypersensitive Sites ◽  
Hypersensitive Sites ◽  
Transcription Factor Occupancy

Abstract Normal differentiation of red cells, platelets and eosinophils from a myeloid progenitor requires expression of the transcription factor GATA1. Moreover, GATA1 expression level influences lineage output; higher levels promote erythromegakaryocytic differentiation and lower levels eosinophil maturation. Conversely, repression of GATA1 expression is required for monocyte/neutrophil development. GATA1 expression is principally controlled transcriptionally. Thus, dissecting the molecular basis of transcriptional control of GATA1 expression will be one important facet in understanding how myeloid lineages are specified. To address this question we sought to identify all DNA sequences important for GATA1 expression. Previous analysis identified 3 murine (m)Gata1 cis-elements (an upstream enhancer, mHS-3.5, a haematopoietic IE promoter and elements in a GATA1 intron, mHS+3.5) conserved in sequence between human(h) and mouse. These studies also suggested additional unidentified elements were required for erythroid and eosinophil GATA1 expression. We compared sequence, mapped DNase I hypersensitive sites (HS) and determined histone H3/H4 acetylation over ~120 kb flanking the hGATA1 locus and corresponding region in mouse to pinpoint cis-elements. Remarkably, despite lying in a ~10 MB conserved syntenic segment, the chromatin structures of both GATA1 loci are strikingly different. Two previously unidentified haematopoietic cis-elements, one in each species (mHS-25 and hHS+14), are not conserved in position and sequence and have enhancer activity in erythroid cells. Chromatin immunoprecipitation studies show both mHS-25 and hHS+14 are bound in vivo in red cells by the transcription factors GATA1, SCL, LMO2, Ldb1. These findings suggest that some cis-elements regulating human and mouse GATA1 genes differ. Further analysis of in vivo transcription factor occupancy at GATA1 cis-elements in primary mouse eosinophils and red cells, megakaryocytic cells (L8057) and control fibroblasts show lineage- and cis-element-specific patterns of regulator binding (see table below). In red cells and megakaryocytes, GATA1, SCL, LMO2 and Ldb1 bind at two regulatory elements (mhHS-25 and mHS-3.5). Interestingly, the megakaryocyte transcriptional regulator Fli1 factor binds to mHS+3.5 specifically in megakaryocytes. In eosinophils, a different pattern of DNase I HS and transcription factor binding is seen. GATA1, PU.1 and C/EBPe (all regulate eosinophil gene expression) bind IE promoter and/or mHS+3.5. Collectively, these results suggest lineage-specific GATA1 expession is dependent on combinations of cis-elements and haematopoietic trans-acting factors that are unique for each lineage. DNase I Hypersensitive sites and transcription factor occupancy at mGATA1 cis-elements. mHS-26/-25* mHS-3.5 mIE mHS+3.5 m: mouse, h: human, *: HS identified in this study, TF: transcription factor Primary erythroid cells HS present, GATA1, SCL, LMO2, Ldb1 HS present, GATA1, SCL, LMO2, Ldb1 HS present, GATA1 HS present, GATA1 Megakaryocytic cells HS present, GATA1, SCL, LMO2, Ldb1 HS present, GATA1, SCL, LMO2, Ldb1 HS present, GATA1 HS present, GATA1 and Fli1 Primary eosinophils HS absent HS present, No TF detected HS present, GATA1 and C/EBPε HS present, GATA1, C/EBP ε and PU.1 Fibroblasts HS absent HS absent HS absent HS absent

scholarly journals Expresso: A database and web server for exploring the interaction of transcription factors and their target genes in Arabidopsis thaliana using ChIP-Seq peak data

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 372 ◽  
Author(s):  
Delasa Aghamirzaie ◽  
Karthik Raja Velmurugan ◽  
Shuchi Wu ◽  
Doaa Altarawy ◽  
Lenwood S. Heath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Data Sets ◽  
Motif Analysis ◽  
Chromatin Immunoprecipitation Sequencing

Motivation: The increasing availability of chromatin immunoprecipitation sequencing (ChIP-Seq) data enables us to learn more about the action of transcription factors in the regulation of gene expression. Even though in vivo transcriptional regulation often involves the concerted action of more than one transcription factor, the format of each individual ChIP-Seq dataset usually represents the action of a single transcription factor. Therefore, a relational database in which available ChIP-Seq datasets are curated is essential. Results: We present Expresso (database and webserver) as a tool for the collection and integration of available Arabidopsis ChIP-Seq peak data, which in turn can be linked to a user’s gene expression data. Known target genes of transcription factors were identified by motif analysis of publicly available GEO ChIP-Seq data sets. Expresso currently provides three services: 1) Identification of target genes of a given transcription factor; 2) Identification of transcription factors that regulate a gene of interest; 3) Computation of correlation between the gene expression of transcription factors and their target genes. Availability: Expresso is freely available at http://bioinformatics.cs.vt.edu/expresso/

scholarly journals Sequence-specific dynamics of DNA response elements and their flanking sites regulate the recognition by AP-1 transcription factors

2020 ◽  
Author(s):  
Johanna Hörberg ◽  
Kevin Moreau ◽  
Anna Reymer
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Binding Sites ◽  
Regulation Of Gene Expression ◽  
Dna Complexes ◽  
Response Element ◽  
Response Elements ◽  
Expression Levels ◽  
The Stability ◽  
Gene Expression Levels

AbstractActivator proteins 1 (AP-1) comprise one of the largest families of eukaryotic basic leucine zipper transcription factors. Despite advances in the characterization of AP-1 DNA-binding sites, our ability to predict new binding sites and explain how the proteins achieve different gene expression levels remains limited. Here we address the role of sequence-specific DNA dynamics for stability and specific binding of AP-1 factors, using microseconds long molecular dynamics simulations. As a model system, we employ yeast AP-1 factor Yap1 binding to three different response elements from two genetic environments. Our data show that Yap1 actively exploits the sequence-specific plasticity of DNA within the response element to form stable protein-DNA complexes. The stability also depends on the four to six flanking nucleotides, adjacent to the response elements. The flanking sequences modulate the conformational adaptability of the response element, making it more shape-efficient to form specific contacts with the protein. Bioinformatics analysis of differential expression of the studied genes supports our conclusions: the stability of Yap1-DNA complexes, modulated by the flanking environment, influences the gene expression levels. Our results provide new insights into mechanisms of protein-DNA recognition and the biological regulation of gene expression levels in eukaryotes.

scholarly journals SWI/SNF Displaces SAGA-Acetylated Nucleosomes

2006 ◽  
Vol 5 (10) ◽  
pp. 1738-1747 ◽  
Author(s):  
Mark Chandy ◽  
José L. Gutiérrez ◽  
Philippe Prochasson ◽  
Jerry L. Workman
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase ◽  
Histone Acetylation ◽  
Chromatin Remodeling ◽  
Binding Sites ◽  
Saga Complex ◽  
Chromatin Remodeling Complex ◽  
Nucleosome Array ◽  
Transcription Activators

ABSTRACT SWI/SNF is a well-characterized chromatin remodeling complex that remodels chromatin by sliding nucleosomes in cis and/or displacing nucleosomes in trans. The latter mechanism has the potential to remove promoter nucleosomes, allowing access to transcription factors and RNA polymerase. In vivo, histone acetylation often precedes apparent nucleosome loss; therefore, we sought to determine whether nucleosomes containing acetylated histones could be displaced by the SWI/SNF chromatin remodeling complex. We found that SAGA-acetylated histones were lost from an immobilized nucleosome array when treated with the SWI/SNF complex. When the nucleosome array was acetylated by SAGA in the presence of bound transcription activators, it generated a peak of acetylation surrounding the activator binding sites. Subsequent SWI/SNF treatment suppressed this acetylation peak. Immunoblots indicated that SWI/SNF preferentially displaced acetylated histones from the array relative to total histones. Moreover, the Swi2/Snf2 bromodomain, an acetyl-lysine binding domain, played a role in the displacement of acetylated histones. These data indicate that targeted histone acetylation by the SAGA complex predisposes promoter nucleosomes for displacement by the SWI/SNF complex.

scholarly journals FOXA1 plays a role in regulating secretoglobin 1a1 expression in the absence of CCAAT/enhancer binding protein activities in lung in vivo

2011 ◽  
Vol 300 (3) ◽  
pp. L441-L452 ◽  
Author(s):  
Taketomo Kido ◽  
Takeshi Tomita ◽  
Minoru Okamoto ◽  
Yan Cai ◽  
Yoshimi Matsumoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Regulation Of Gene Expression ◽  
Dominant Negative ◽  
Clara Cell ◽  
Small Molecular Weight ◽  
Dominant Negative Form

Secretoglobin (SCGB) 1A1, also called Clara cell secretor protein (CCSP) or Clara cell-specific 10-kDa protein (CC10), is a small molecular weight secreted protein mainly expressed in lung, with anti-inflammatory/immunomodulatory properties. Previous in vitro studies demonstrated that CCAAT/enhancer-binding proteins (C/EBPs) are the major transcription factors for the regulation of Scbg1a1 gene expression, whereas FOXA1 had a minimum effect on the transcription. To determine the in vivo role of C/EBPs in the regulation of SCGB1A1 expression, experiments were performed in which A-C/EBP, a dominant-negative form of C/EBP that interferes with DNA binding activities of all C/EBPs, was specifically expressed in lung. Surprisingly, despite the in vitro findings, expression of SCGB1A1 mRNA was not decreased in vivo in the absence of C/EBPs. This may be due to a compensatory role assumed by FOXA1 in the regulation of Scgb1a1 gene expression in lung in the absence of active C/EBPs. This disconnect between in vitro and in vivo results underscores the importance of studies using animal models to determine the role of specific transcription factors in the regulation of gene expression in intact multicellular complex organs such as lung.

scholarly journals Understanding Transcription Factor Regulation by Integrating Gene Expression and DNase I Hypersensitive Sites

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Guohua Wang ◽  
Fang Wang ◽  
Qian Huang ◽  
Yu Li ◽  
Yunlong Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Dna Sequences ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Transcription Factor Binding ◽  
Interferon Treatment ◽  
Factor Binding ◽  
Hypersensitive Sites

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.

scholarly journals A Lipopolysaccharide-Specific Enhancer Complex Involving Ets, Elk-1, Sp1, and CREB Binding Protein and p300 Is Recruited to the Tumor Necrosis Factor Alpha Promoter In Vivo

2000 ◽  
Vol 20 (16) ◽  
pp. 6084-6094 ◽  
Author(s):  
Eunice Y. Tsai ◽  
James V. Falvo ◽  
Alla V. Tsytsykova ◽  
Amy K. Barczak ◽  
Andreas M. Reimold ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Binding Sites ◽  
Tumor Necrosis ◽  
Creb Binding Protein ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT The tumor necrosis factor alpha (TNF-α) gene is rapidly activated by lipopolysaccharide (LPS). Here, we show that extracellular signal-regulated kinase (ERK) kinase activity but not calcineurin phosphatase activity is required for LPS-stimulated TNF-α gene expression. In LPS-stimulated macrophages, the ERK substrates Ets and Elk-1 bind to the TNF-α promoter in vivo. Strikingly, Ets and Elk-1 bind to two TNF-α nuclear factor of activated T cells (NFAT)-binding sites, which are required for calcineurin and NFAT-dependent TNF-α gene expression in lymphocytes. The transcription factors ATF-2, c-jun, Egr-1, and Sp1 are also inducibly recruited to the TNF-α promoter in vivo, and the binding sites for each of these activators are required for LPS-stimulated TNF-α gene expression. Furthermore, assembly of the LPS-stimulated TNF-α enhancer complex is dependent upon the coactivator proteins CREB binding protein and p300. The finding that a distinct set of transcription factors associates with a fixed set of binding sites on the TNF-α promoter in response to LPS stimulation lends new insights into the mechanisms by which complex patterns of gene regulation are achieved.

scholarly journals Chromatin Remodeling Complex Interacts with ADD1/SREBP1c To Mediate Insulin-Dependent Regulation of Gene Expression

2006 ◽  
Vol 27 (2) ◽  
pp. 438-452 ◽  
Author(s):  
Yun Sok Lee ◽  
Dong Hyun Sohn ◽  
Daehee Han ◽  
Han-Woong Lee ◽  
Rho Hyun Seong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Sensitivity ◽  
Chromatin Remodeling ◽  
Target Gene ◽  
Regulation Of Gene Expression ◽  
Whole Body ◽  
Gene Promoters ◽  
Proteolytic Activation ◽  
Insulin Dependent

ABSTRACT Insulin plays a critical role in whole-body energy homeostasis by regulating lipid and glucose metabolism. In fat and liver tissues, ADD1/SREBP1c is a key transcription factor to mediate insulin-dependent regulation of gene expression. Although transcriptional and proteolytic activation of ADD1/SREBP1c has been studied intensively, the mechanism by which insulin regulates expression of its target genes with ADD1/SREBP1c at the chromatin level is unclear. Here, we reveal that SWI/SNF chromatin remodeling factors interact with the ADD1/SREBP1c and actively regulate insulin-dependent gene expression. Insulin enhanced recruitment of SWI/SNF chromatin remodeling factors to its target gene promoters with concomitant changes in the chromatin structures as well as gene expression. Furthermore, in vivo overexpression of BAF155/SRG3, a component of the SWI/SNF complex, substantially promoted insulin target gene expression and insulin sensitivity. Taken together, our results suggest that the SWI/SNF chromatin remodeling complexes confer not only insulin-dependent gene expression but also insulin sensitivity in vivo via interaction with ADD1/SREBP1c.

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