scholarly journals Transcription factor target site search and gene regulation in a background of unspecific binding sites

2018 ◽  
Vol 454 ◽  
pp. 91-101 ◽  
Author(s):  
J. Hettich ◽  
J.C.M. Gebhardt
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Binding Sites ◽  
Target Site ◽  
Site Search ◽  
Transcription Factor Target ◽  
Unspecific Binding

scholarly journals Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites

2021 ◽  
Vol 49 (7) ◽  
pp. 3856-3875
Author(s):  
Marina Kulik ◽  
Melissa Bothe ◽  
Gözde Kibar ◽  
Alisa Fuchs ◽  
Stefanie Schöne ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Dna Binding ◽  
Receptor Binding ◽  
Binding Sites ◽  
Specific Gene ◽  
Functional Diversification ◽  
Enhancer Activity ◽  
Sequence Composition

Abstract The glucocorticoid (GR) and androgen (AR) receptors execute unique functions in vivo, yet have nearly identical DNA binding specificities. To identify mechanisms that facilitate functional diversification among these transcription factor paralogs, we studied them in an equivalent cellular context. Analysis of chromatin and sequence suggest that divergent binding, and corresponding gene regulation, are driven by different abilities of AR and GR to interact with relatively inaccessible chromatin. Divergent genomic binding patterns can also be the result of subtle differences in DNA binding preference between AR and GR. Furthermore, the sequence composition of large regions (>10 kb) surrounding selectively occupied binding sites differs significantly, indicating a role for the sequence environment in guiding AR and GR to distinct binding sites. The comparison of binding sites that are shared shows that the specificity paradox can also be resolved by differences in the events that occur downstream of receptor binding. Specifically, shared binding sites display receptor-specific enhancer activity, cofactor recruitment and changes in histone modifications. Genomic deletion of shared binding sites demonstrates their contribution to directing receptor-specific gene regulation. Together, these data suggest that differences in genomic occupancy as well as divergence in the events that occur downstream of receptor binding direct functional diversification among transcription factor paralogs.

scholarly journals WAPL maintains dynamic cohesin to preserve lineage specific distal gene regulation

2019 ◽  
Author(s):  
Ning Qing Liu ◽  
Michela Maresca ◽  
Teun van den Brand ◽  
Luca Braccioli ◽  
Marijne M.G.A. Schijns ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcription Factor ◽  
Binding Sites ◽  
Transcription Factor Binding ◽  
Ctcf Binding ◽  
Release Factor ◽  
Factor Binding ◽  
Active Enhancer ◽  
Lineage Specific Genes

SUMMARYThe cohesin complex plays essential roles in sister chromatin cohesin, chromosome organization and gene expression. The role of cohesin in gene regulation is incompletely understood. Here, we report that the cohesin release factor WAPL is crucial for maintaining a pool of dynamic cohesin bound to regions that are associated with lineage specific genes in mouse embryonic stem cells. These regulatory regions are enriched for active enhancer marks and transcription factor binding sites, but largely devoid of CTCF binding sites. Stabilization of cohesin, which leads to a loss of dynamic cohesin from these regions, does not affect transcription factor binding or active enhancer marks, but does result in changes in promoter-enhancer interactions and downregulation of genes. Acute cohesin depletion can phenocopy the effect of WAPL depletion, showing that cohesin plays a crucial role in maintaining expression of lineage specific genes. The binding of dynamic cohesin to chromatin is dependent on the pluripotency transcription factor OCT4, but not NANOG. Finally, dynamic cohesin binding sites are also found in differentiated cells, suggesting that they represent a general regulatory principle. We propose that cohesin dynamically binding to regulatory sites creates a favorable spatial environment in which promoters and enhancers can communicate to ensure proper gene expression.HIGHLIGHTSThe cohesin release factor WAPL is crucial for maintaining a pluripotency-specific phenotype.Dynamic cohesin is enriched at lineage specific loci and overlaps with binding sites of pluripotency transcription factors.Expression of lineage specific genes is maintained by dynamic cohesin binding through the formation of promoter-enhancer associated self-interaction domains.CTCF-independent cohesin binding to chromatin is controlled by the pioneer factor OCT4.

scholarly journals Different Functional Gene Clusters in Yeast have Different Spatial Distributions of the Transcription Factor Binding Sites

2011 ◽  
Vol 5 ◽  
pp. BBI.S6362 ◽  
Author(s):  
Wei-Sheng Wu
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Spatial Distribution ◽  
Transcription Factors ◽  
Binding Sites ◽  
Transcription Factor Binding Sites ◽  
Gene Clusters ◽  
Functional Gene ◽  
Spatial Distributions ◽  
Factor Binding

Transcription factors control gene expression by binding to short specific DNA sequences, called transcription factor binding sites (TFBSs), in the promoter of a gene. Thus, studying the spatial distribution of TFBSs in the promoters may provide insights into the molecular mechanisms of gene regulation. I developed a method to construct the spatial distribution of TFBSs for any set of genes of interest. I found that different functional gene clusters have different spatial distributions of TFBSs, indicating that gene regulation mechanisms may be very different among different functional gene clusters. I also found that the binding sites for different transcription factors (TFs) may have different spatial distributions: a sharp peak, a plateau or no dominant single peak. The spatial distributions of binding sites for many TFs derived from my analyses are valuable prior information for TFBS prediction algorithm because different regions of a promoter can assign different possibilities for TFBS occurrence.

scholarly journals A systematic genome-wide account of binding sites for the model transcription factor Gcn4

2021 ◽  
pp. gr.276080.121
Author(s):  
Christopher T Coey ◽  
David J. Clark
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Binding Sites ◽  
Yeast Genome ◽  
High Affinity ◽  
First Approximation ◽  
Genome Wide ◽  
Insight Into

Sequence-specific DNA-binding transcription factors are central to gene regulation. They are often associated with consensus binding sites that predict far more genomic sites than are bound in vivo. One explanation is that most sites are blocked by nucleosomes, such that only sites in nucleosome-depleted regulatory regions are bound. We compared the binding of the yeast transcription factor Gcn4 in vivo using published ChIP-seq data (546 sites) and in vitro, using a modified SELEX method ("G-SELEX"), which utilizes short genomic DNA fragments to quantify binding at all sites. We confirm that Gcn4 binds strongly to an AP-1-like sequence (TGACTCA) and weakly to half-sites. However, Gcn4 binds only some of the 1078 exact matches to this sequence, even in vitro. We show that there are only 166 copies of the high-affinity RTGACTCAY site (exact match) in the yeast genome, all occupied in vivo, largely independently of whether they are located in nucleosome-depleted or nucleosomal regions. Generally, RTGACTCAR/YTGACTCAY sites are bound much more weakly and YTGACTCAR sites are unbound, with biological implications for determining induction levels. We conclude that, to a first approximation, Gcn4 binding can be predicted using the high-affinity site, without reference to chromatin structure. We propose that transcription factor binding sites should be defined more precisely using quantitative data, allowing more accurate genome-wide prediction of binding sites and greater insight into gene regulation.

scholarly journals Androgen and glucocorticoid receptor direct distinct transcriptional programs by receptor-specific and shared DNA binding sites

2020 ◽  
Author(s):  
Marina Borschiwer ◽  
Melissa Bothe ◽  
Gözde Kibar ◽  
Alisa Fuchs ◽  
Stefanie Schöne ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Dna Binding ◽  
Receptor Binding ◽  
Binding Sites ◽  
Specific Gene ◽  
Functional Diversification ◽  
Enhancer Activity ◽  
Sequence Composition

AbstractThe glucocorticoid (GR) and androgen (AR) receptors execute unique functions in vivo, yet have nearly identical DNA binding specificities. To identify mechanisms that facilitate functional diversification among these transcription factor paralogs, we studied AR and GR in an equivalent cellular context. Analysis of chromatin and sequence features suggest that divergent binding, and corresponding gene regulation, are driven by different abilities of AR and GR to interact with relatively inaccessible chromatin. Divergent genomic binding patterns can also be the results of subtle differences in DNA binding preference between AR and GR. Furthermore, the sequence composition of large regions (>10 kb) surrounding selectively occupied binding sites differs significantly, indicating a role for the sequence environment in selectively guiding AR and GR to distinct binding sites. The comparison of binding sites that are shared between AR and GR shows that the specificity paradox can also be resolved by differences in the events that occur downstream of receptor binding. Specifically, we find that shared binding sites display receptor-specific enhancer activity, cofactor recruitment and changes in histone modifications. Genomic deletion of shared binding sites demonstrates their contribution to directing receptor-specific gene regulation. Together, these data suggest that differences in genomic occupancy as well as divergence in the events that occur downstream of receptor binding direct functional diversification among transcription factor paralogs.

scholarly journals Identification of bacterial virulence factors based on an integration of experimental and in silico transcription factor target discovery

2020 ◽  
Author(s):  
P. V. Vychyk ◽  
Y. A. Nikolaichik
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
In Silico ◽  
Soft Rot ◽  
Bacterial Virulence ◽  
Dickeya Dadantii ◽  
Soft Rot Disease ◽  
Transcription Factor Target ◽  
Rot Disease

In silico transcription factors binding sites analysis in Dickeya dadantii genome matches published experimental results and predicts new regulators for genes inducing soft-rot disease in plants.

scholarly journals Anecdotes, data and regulatory modules

2006 ◽  
Vol 2 (3) ◽  
pp. 431-434 ◽  
Author(s):  
James E Balmer ◽  
Rune Blomhoff
Keyword(s):  
Gene Regulation ◽  
Transcription Factor ◽  
Binding Sites ◽  
General Rule ◽  
Phylogenetic Footprinting ◽  
Developmental Gene ◽  
Regulatory Modules ◽  
Developmental Gene Regulation ◽  
To Come ◽  
Do So

Beginning in the late 1980s, Eric Davidson's group at Cal Tech developed a modularity hypothesis of developmental gene regulation, showing that in an expanding number of cases, particular aspects of development were governed by compact ‘modules’ of transcription factor binding sites (TFBSs), and that these modules were separable, complex and interconnected. Davidson made no attempt to further generalize the hypothesis, but others took up the idea, transported it out of development and extended it to a general rule of clustering. Despite such misbegotten origins, the ‘extended’ modularity hypothesis—that TFBSs in general tend to come in compact clusters—has been highly productive, yet it has never been challenged with a large, diverse and unbiased dataset to see how universal it actually is. The aim of the present paper is to do so. Applying human–mouse–rat phylogenetic footprinting to neighbourhoods of a diverse set of TFBSs, including both developmental and non-developmental signals, we find that the extended hypothesis holds in at least 93.5% of cases. Based on this particular sample, we found a mean module length of 609 nucleotides containing, on an average, 24.5 presumptive regulatory signals of length greater than 5 and averaging 8.5 nucleotides each.

scholarly journals AddTag, a two-step approach with supporting software package that facilitates CRISPR/Cas-mediated precision genome editing

2021 ◽  
Author(s):  
Thaddeus D Seher ◽  
Namkha Nguyen ◽  
Diana Ramos ◽  
Priyanka Bapat ◽  
Clarissa J Nobile ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Genome Editing ◽  
Binding Sites ◽  
Software Package ◽  
Gene Editing ◽  
Target Site ◽  
Genomic Features ◽  
Single Base ◽  
Gene Complementation ◽  
Single Base Pair

Abstract CRISPR/Cas-induced genome editing is a powerful tool for genetic engineering, however targeting constraints limit which loci are editable with this method. Since the length of a DNA sequence impacts the likelihood it overlaps a unique target site, precision editing of small genomic features with CRISPR/Cas remains an obstacle. We introduce a two-step genome editing strategy that virtually eliminates CRISPR/Cas targeting constraints and facilitates precision genome editing of elements as short as a single base-pair at virtually any locus in any organism that supports CRISPR/Cas-induced genome editing. Our two-step approach first replaces the locus of interest with an “AddTag” sequence, which is subsequently replaced with any engineered sequence, and thus circumvents the need for direct overlap with a unique CRISPR/Cas target site. In this study, we demonstrate the feasibility of our approach by editing transcription factor binding sites within Candida albicans that could not be targeted directly using the traditional gene editing approach. We also demonstrate the utility of the AddTag approach for combinatorial genome editing and gene complementation analysis, and we present a software package that automates the design of AddTag editing.

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