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

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

PROVIDER: PRJNA680044 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13106640_1.fastq.gz	Fastqsanger.gz
	SRR13106640_2.fastq.gz	Fastqsanger.gz
	SRR13106641_1.fastq.gz	Fastqsanger.gz
	SRR13106641_2.fastq.gz	Fastqsanger.gz
	SRR13106642_1.fastq.gz	Fastqsanger.gz

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

Project description:The coactivator p300/CBP regulates genes by facilitating the assembly of transcriptional machinery and by acetylating histones and other factors. However, it remains mostly unclear how both functions of p300 are dynamically coordinated during gene control. Here, we showed that p300 appears to orchestrate two functions through the formation of dynamic co-condensates with certain transcription factors (TFs), which is mediated by the interactions between the TF’s trans-activation domain (TAD) and the intrinsically disordered regions (IDRs) of p300. Co-condensation enables spatially defined, all-or-none activation of p300’s catalytic activity, priming the recruitment of other coactivators including Brd4. We further revealed that co-condensation modulates transcriptional initiation rate and burst duration of target genes, underlying nonlinear and cooperative gene regulatory functions. Intriguingly, such modulation is consistent with how p300 shapes transcriptional bursting kinetics globally. Together, complementary lines of evidence suggest a new p300-mediated gene control mechanism, where TF and p300 co-condensation contributes to transcriptional bursting regulation and cooperative gene control.

2022-02-28 | GSE161958 | GEO

Coactivator condensation drives lineage specification

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Coactivator condensation drives cell lineage specification

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Coactivator condensation at super-enhancers links phase separation and gene control

Project description:Coactivator condensation at super-enhancers links phase separation and gene control

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Coactivator condensation drives lineage specification

Project description:During development, cells make switch-like decisions to activate the expression of new gene programs leading to lineage specification1. The mechanisms underlying these decisive choices remain unclear2. Here we find that Myocardin (MYOCD), a cardiomyocyte and smooth muscle cell-specific transcriptional coactivator3-6, activates lineage-specific gene programs by concentration-dependent and switch-like formation of nuclear condensates. While compartmentalization of the transcriptional machinery by condensates has been associated with gene activation7,8, directly linking the two processes has been a major challenge for the field9,10. By modeling the natural changes in MYOCD concentration during development, coupled with quantitative fluorescence microscopy, single-cell resolution reporter assays, and cellular differentiation assays, we demonstrate that condensate formation is directly linked to transcriptional activation and lineage specification. During cardiomyocyte and smooth muscle cell differentiation, the formation of MYOCD condensates precedes activation of cell identity genes and these condensates are present at sites of cell identity gene transcription. MYOCD condensates form, activate gene expression, and specify cell state at critical concentration thresholds, dependent upon the C-terminal disordered region of MYOCD. Disrupting condensate formation by manipulating the sequence of this region impairs gene activation which can be rescued by replacing this region with condensate-forming disordered regions from functionally unrelated proteins. These results demonstrate that coactivator condensation at critical concentrations enables switch-like changes in gene expression programs crucial for lineage specification.

2024-03-20 | GSE235928 | GEO

Regulation of stochastic gene bursting by chromatin-independent acetylation

Project description:Stochastic transcriptional bursting is now recognized as a universal property of gene expression. While different genes exhibit distinct bursting patterns, the molecular basis for differences in bursting are largely unknown. We have developed and applied a high-throughput-imaging based screening strategy to identify cellular factors and mechanisms that determine the bursting behavior of human genes. Focusing on epigenetic regulators, we find that global acetylation is the strongest acute modulator of burst frequency, size and heterogeneity of bursting. Acetylation similarly affected the Off-time but On-time changes were gene-specific. These effects were not strongly linked to promoter acetylation, which did not correlate with bursting properties and forced promoter acetylation altered bursting for only some genes. Instead, we identified acetylation of the Integrator complex as a key determinant of gene bursting with elevated Integrator acetylation leading to faster bursting. Taken together our results suggest a dominant role of non-histone proteins in determining gene bursting properties and they identify non-epigenetic acetylation of a transcription cofactor as an allosteric modulator of bursting via a pause-release related bursting checkpoint

2024-06-26 | GSE254866 | GEO

Coactivator condensation at super-enhancers links phase separation and gene control (RNA-Seq)

Project description:Coactivator condensation at super-enhancers links phase separation and gene control (RNA-Seq)

| PRJNA449067 | ENA

Coactivator condensation at super-enhancers links phase separation and gene control (ChIP-Seq)

Project description:Coactivator condensation at super-enhancers links phase separation and gene control (ChIP-Seq)

| PRJNA449065 | ENA

Role of RelA:CBP/p300 interaction on RelA-activated genes

Project description:A structure-function study of NF-kB subunit RelA and coactivator CBP/p300 interaction reveals the critical role of CBP/p300 in recruitment of RelA to its target promoter site.

2013-09-09 | GSE46213 | GEO

Role of RelA:CBP/p300 interaction on RelA-activated genes

Project description:A structure-function study of NF-kB subunit RelA and coactivator CBP/p300 interaction reveals the critical role of CBP/p300 in recruitment of RelA to its target promoter site. mRNA profiles of unstimulated or stimulated with TNFa rela-/- MEF reconstituted with RelA wild type or mutants were generated by deep sequencing, in duplicate

2013-09-09 | E-GEOD-46213 | biostudies-arrayexpress

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