Co-condensation between transcription factor and coactivator p300 modulates transcriptional bursting kinetics

2021 ◽  
Author(s):  
Liang Ma ◽  
Zeyue Gao ◽  
Jiegen Wu ◽  
Bijunyao Zhong ◽  
Yuchen Xie ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Bursting ◽  
Coactivator P300

Dynamic epistasis analysis reveals how chromatin remodeling regulates transcriptional bursting

2021 ◽  
Author(s):  
Ineke Brouwer ◽  
Emma Kerklingh ◽  
Fred van Leeuwen ◽  
Tineke L Lenstra
Keyword(s):  
Transcription Factor ◽  
Chromatin Remodeling ◽  
Single Molecule ◽  
Binding Sites ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Nucleosome Remodeling ◽  
Epistasis Analysis ◽  
Transcriptional Bursting ◽  
Kinetics Of

Transcriptional bursting has been linked to the stochastic positioning of nucleosomes. However, how bursting is regulated by remodeling of promoter nucleosomes is unknown. Here, we use single-molecule live-cell imaging of GAL10 transcription in budding yeast to measure how transcriptional bursting changes upon single and double perturbations of chromatin remodeling factors, the transcription factor Gal4 and preinitiation complex (PIC) components. Using dynamic epistasis analysis, we reveal how remodeling of different nucleosomes regulates individual transcriptional bursting parameters. At the nucleosome covering the Gal4 binding sites, RSC acts synergistically with Gal4 binding to facilitate each burst. Conversely, nucleosome remodeling at the TATA box controls only the first burst upon galactose induction. In the absence of remodelers, nucleosomes at canonical TATA boxes are displaced by TBP binding to allow for transcription activation. Overall, our results reveal how promoter nucleosome remodeling, together with transcription factor and PIC binding regulates the kinetics of transcriptional bursting.

scholarly journals The transcription factor activity gradient (TAG) model: contemplating a contact-independent mechanism for enhancer–promoter communication

2021 ◽  
Author(s):  
Jonathan P. Karr ◽  
John J. Ferrie ◽  
Robert Tjian ◽  
Xavier Darzacq
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Regulatory Elements ◽  
Transcription Factor Activity ◽  
Factor Activity ◽  
New Model ◽  
Unresolved Question ◽  
Regulatory Information ◽  
Independent Mechanism ◽  
Coactivator P300

How distal cis-regulatory elements (e.g., enhancers) communicate with promoters remains an unresolved question of fundamental importance. Although transcription factors and cofactors are known to mediate this communication, the mechanism by which diffusible molecules relay regulatory information from one position to another along the chromosome is a biophysical puzzle—one that needs to be revisited in light of recent data that cannot easily fit into previous solutions. Here we propose a new model that diverges from the textbook enhancer–promoter looping paradigm and offer a synthesis of the literature to make a case for its plausibility, focusing on the coactivator p300.

scholarly journals Single-molecule imaging reveals the interplay between transcription factors, nucleosomes, and transcriptional bursting

2018 ◽  
Author(s):  
Benjamin T. Donovan ◽  
Anh Huynh ◽  
David A. Ball ◽  
Michael G. Poirier ◽  
Daniel R. Larson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Single Molecule ◽  
Target Genes ◽  
Burst Size ◽  
Yeast Cells ◽  
Single Molecule Imaging ◽  
Transcriptional Bursting

SummaryTranscription factors show rapid and reversible binding to chromatin in living cells, and transcription occurs in sporadic bursts, but how these phenomena are related is unknown. Using a combination of in vitro and in vivo single-molecule imaging approaches, we directly correlated binding of the transcription factor Gal4 with the transcriptional bursting kinetics of the Gal4 target genes GAL3 and GAL10 in living yeast cells. We find that Gal4 dwell times sets the transcriptional burst size. Gal4 dwell time depends on the affinity of the binding site and is reduced by orders of magnitude by nucleosomes. Using a novel imaging platform, we simultaneously tracked transcription factor binding and transcription at one locus, revealing the timing and correlation between Gal4 binding and transcription. Collectively, our data support a model where multiple polymerases initiate during a burst as long as the transcription factor is bound to DNA, and a burst terminates upon transcription factor dissociation.

A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis

Nature ◽  
2002 ◽  
Vol 419 (6908) ◽  
pp. 738-743 ◽  
Author(s):  
Lawryn H. Kasper ◽  
Fayçal Boussouar ◽  
Paul A. Ney ◽  
Carl W. Jackson ◽  
Jerold Rehg ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factor Binding ◽  
Factor Binding ◽  
Binding Surface ◽  
Coactivator P300

scholarly journals Transcriptional Bursting and Co-bursting Regulation by Steroid Hormone Release Pattern and Transcription Factor Mobility

2019 ◽  
Vol 75 (6) ◽  
pp. 1161-1177.e11 ◽  
Author(s):  
Diana A. Stavreva ◽  
David A. Garcia ◽  
Gregory Fettweis ◽  
Prabhakar R. Gudla ◽  
George F. Zaki ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Steroid Hormone ◽  
Hormone Release ◽  
Factor Mobility ◽  
Release Pattern ◽  
Transcriptional Bursting

scholarly journals Naphthol AS-E Phosphate Inhibits the Activity of the Transcription Factor Myb by Blocking the Interaction with the KIX Domain of the Coactivator p300

2015 ◽  
Vol 14 (6) ◽  
pp. 1276-1285 ◽  
Author(s):  
Sagar Uttarkar ◽  
Sandeep Dukare ◽  
Bertan Bopp ◽  
Michael Goblirsch ◽  
Joachim Jose ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Kix Domain ◽  
Coactivator P300

scholarly journals Orphan Nuclear Receptor Small Heterodimer Partner, a Novel Corepressor for a Basic Helix-Loop-Helix Transcription Factor BETA2/NeuroD

2004 ◽  
Vol 18 (4) ◽  
pp. 776-790 ◽  
Author(s):  
Joon-Young Kim ◽  
Khoi Chu ◽  
Han-Jong Kim ◽  
Hyun-A Seong ◽  
Ki-Cheol Park ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Nuclear Receptor ◽  
Transcriptional Activity ◽  
Orphan Nuclear Receptor ◽  
Small Heterodimer Partner ◽  
Basic Helix Loop Helix ◽  
Helix Loop Helix ◽  
E Box ◽  
Coactivator P300

Abstract Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA binding domain (DBD) and represses the transcriptional activity of various nuclear receptors. In this study, we examined the novel cross talk between SHP and BETA2/NeuroD, a basic helix-loop-helix transcription factor. In vitro and in vivo protein interaction studies showed that SHP physically interacts with BETA2/NeuroD, but not its heterodimer partner E47. Moreover, confocal microscopic study and immunostaining results demonstrated that SHP colocalized with BETA2 in islets of mouse pancreas. SHP inhibited BETA2/NeuroD-dependent transactivation of an E-box reporter, whereas SHP was unable to repress the E47-mediated transactivation and the E-box mutant reporter activity. In addition, SHP repressed the BETA2-dependent activity of glucokinase and cyclin-dependent kinase inhibitor p21 gene promoters. Gel shift and in vitro protein competition assays indicated that SHP inhibits neither dimerization nor DNA binding of BETA2 and E47. Rather, SHP directly repressed BETA2 transcriptional activity and p300-enhanced BETA2/NeuroD transcriptional activity by inhibiting interaction between BETA2 and coactivator p300. We also showed that C-terminal repression domain within SHP is also required for BETA2 repression. However, inhibition of BETA2 activity was not observed by naturally occurring human SHP mutants that cannot interact with BETA2/NeuroD. Taken together, these results suggest that SHP acts as a novel corepressor for basic helix-loop-helix transcription factor BETA2/NeuroD by competing with coactivator p300 for binding to BETA2/NeuroD and by its direct transcriptional repression function.

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