scholarly journals Principles of dimer-specific gene regulation revealed by a comprehensive characterization of NF-κB family DNA binding

2011 ◽  
Vol 13 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Trevor Siggers ◽  
Abraham B Chang ◽  
Ana Teixeira ◽  
Daniel Wong ◽  
Kevin J Williams ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Dna Binding ◽  
Specific Gene ◽  
Comprehensive Characterization

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 DNA-binding landscape of IRF3, IRF5 and IRF7 dimers: implications for dimer-specific gene regulation

2018 ◽  
Vol 46 (5) ◽  
pp. 2509-2520 ◽  
Author(s):  
Kellen K Andrilenas ◽  
Vijendra Ramlall ◽  
Jesse Kurland ◽  
Brandon Leung ◽  
Allen G Harbaugh ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Dna Binding ◽  
Specific Gene

scholarly journals Functional analysis of the endothelial cell-specific Tie2/Tek promoter identifies unique protein-binding elements

1998 ◽  
Vol 330 (1) ◽  
pp. 335-343 ◽  
Author(s):  
M. Bahaa FADEL ◽  
C. Stephane BOUTET ◽  
Thomas QUERTERMOUS
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Dna Binding ◽  
Protein Binding ◽  
Dna Sequences ◽  
Molecular Basis ◽  
Proximal Promoter ◽  
Specific Gene ◽  
Specific Gene Expression

To investigate the molecular basis of endothelial cell-specific gene expression, we have examined the DNA sequences and the cognate DNA-binding proteins that mediate transcription of the murine tie2/tek gene. Reporter transfection experiments conformed with earlier findings in transgenic mice, indicating that the upstream promoter of Tie2/Tek is capable of activating transcription in an endothelial cell-specific fashion. These experiments have also allowed the identification of a single upstream inhibitory region (region I) and two positive regulatory regions (regions U and A) in the proximal promoter. Electrophoretic mobility-shift assays have allowed further characterization of three novel DNA-binding sequences associated with these regions and have provided preliminary characterization of the protein factors binding to these elements. Two of the elements (U and A) confer increased transcription on a heterologous promoter, with element U functioning in an endothelial-cell-selective manner. By employing embryonic endothelial-like yolk sac cells in parallel with adult-derived endothelial cells, we have identified differences in functional activity and protein binding that may reflect mechanisms for specifying developmental regulation of tie2/tek expression. Further study of the DNA and protein elements characterized in these experiments is likely to provide new insight into the molecular basis of developmental- and cell-specific gene expression in the endothelium.

Transcription factors: specific DNA binding and specific gene regulation

2014 ◽  
Vol 30 (6) ◽  
pp. 211-219 ◽  
Author(s):  
Anne-Laure Todeschini ◽  
Adrien Georges ◽  
Reiner A. Veitia
Keyword(s):  
Gene Regulation ◽  
Transcription Factors ◽  
Dna Binding ◽  
Specific Gene

Selective DNA binding by the androgen receptor as a mechanism for hormone-specific gene regulation

2001 ◽  
Vol 76 (1-5) ◽  
pp. 23-30 ◽  
Author(s):  
F. Claessens ◽  
G. Verrijdt ◽  
E. Schoenmakers ◽  
A. Haelens ◽  
B. Peeters ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Androgen Receptor ◽  
Dna Binding ◽  
Specific Gene ◽  
Selective Dna Binding

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 Characterization of consensus operator site for Streptococcus pneumoniae copper repressor, CopY

2019 ◽  
Author(s):  
Henrik O’Brien ◽  
Joseph W. Alvin ◽  
Sanjay V. Menghani ◽  
Koenraad Van Doorslaer ◽  
Michael D. L. Johnson
Keyword(s):  
Gene Regulation ◽  
Streptococcus Pneumoniae ◽  
Dna Binding ◽  
Consensus Sequence ◽  
Copper Chaperone ◽  
Enterococcus Hirae ◽  
Bacterial Gene ◽  
Operator Sequence ◽  
Operator Site

ABSTRACTCopper is broadly toxic to bacteria. As such, bacteria have evolved specialized copper export systems (cop operons) often consisting of a DNA-binding/copper-responsive regulator (which can be a repressor or activator), a copper chaperone, and a copper exporter. For those bacteria using DNA-binding copper repressors, few studies have examined the regulation of this operon regarding the operator DNA sequence needed for repression. In Streptococcus pneumoniae (the pneumococcus), CopY is the copper repressor for the cop operon. Previously, these homologs have been characterized to bind a 10-base consensus sequence T/GACAnnTGTA. Here, we bioinformatically and empirically characterize these operator sites across species using S. pneumoniae CopY as a guide for binding. By examining the 21-base repeat operators for the pneumococcal cop operon and comparing binding of recombinant CopY to this, and the operator sites found in Enterococcus hirae, we show using biolayer interferometry that the T/GACAnnTGTA sequence is essential to binding, but it is not sufficient. We determine a more comprehensive S. pneumoniae CopY operator sequence to be RnYKACAAATGTARnY (where “R” is purine, “Y” is pyrimidine, and “K” is either G or T) binding with an affinity of 28 nM. We further propose that the cop operon operator consensus site of pneumococcal homologs be RnYKACAnnYGTARnY. This study illustrates the necessity to explore bacterial operator sites further to better understand bacterial gene regulation.

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