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Transcription factors activate genes through the phase separation capacity of their activation domains

ABSTRACT: Transcription factors activate genes through the phase separation capacity of their activation domains

PROVIDER: PRJNA493113 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7902570.fastq.gz	Fastqsanger.gz
	SRR7902720.fastq.gz	Fastqsanger.gz
	SRR7902571.fastq.gz	Fastqsanger.gz
	SRR7902721.fastq.gz	Fastqsanger.gz
	SRR7902572.fastq.gz	Fastqsanger.gz

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Transcription factors activate genes through the phase separation capacity of their activation domains [RNA-seq]

Project description:Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well- characterized, but little is known about the mechanisms by which ADs effect gene activation. Here we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation.

2018-10-26 | GSE120474 | GEO

Transcription factors activate genes through the phase separation capacity of their activation domains [ChIP-seq]

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Transcription factors activate genes through the phase separation capacity of their activation domains [ChIP-seq]

Project description:Transcription factors activate genes through the phase separation capacity of their activation domains [ChIP-seq]

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Transcription factors activate genes through the phase separation capacity of their activation domains [RNA-seq]

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CPSF6 regulates alternative polyadenylation and proliferation of cancer cell through phase separation

Project description:In order to explore the impact of phase separation of CPSF6 on APA, we identified the structural domains that affect its phase separation formation and performed mutations. In addition, we also found that the phosphorylation of CPSF6 can also affect its phase separation effect, and identified key kinases. We performed IVT-SAPAS sequencing on both cases mentioned above.

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Aberrant phase separation of transcription factors in human developmental disorders

Project description:Components of the transcription machinery can undergo liquid-liquid phase separation, but the functional importance of phase-separated condensates in transcriptional control is not well understood. Here we report that disease-causing mutations in several transcription factors (TFs) alter the phase separation capacity of those TFs. We first demonstrate that the Hoxd13 TF, and its intrinsically disordered N-terminus form phase-separated condensates. Expansions of a polyalanine repeat, which cause hereditary synpolydactyly in humans, facilitate phase separation of Hoxd13, and alter the transcriptional program of several cell types in a cell-specific manner in vivo. Disease-associated expansions of aminoacid repeats in intrinsically disordered regions of other TFs were similarly found to alter phase separation. These results suggest that aberrant phase separation of transcriptional regulators may underlie a spectrum of human pathologies. The paper is available at https://doi.org/10.1016/j.cell.2020.04.018

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Filamentation and Biofilm Formation are Regulated by the Phase-Separation Capacity of Network Transcription Factors in Candida albicans

Project description:The ability of the fungus Candida albicans to filament and form biofilms contributes to its burden as a leading cause of hospital-acquired infections. Biofilm development involves an interconnected transcriptional regulatory network (TRN) consisting of nine transcription factors (TFs) that bind both to their own regulatory regions and to those of the other network TFs. Here, we show that seven of the nine TFs in the C. albicans biofilm network contain prion-like domains (PrLDs) that have been linked to the ability to form phase-separated condensates. Construction of PrLD mutants in four biofilm TFs reveals that these domains are essential for filamentation and biofilm formation in C. albicans. Moreover, biofilm PrLDs promote the formation of phase-separated condensates in the nuclei of live cells, and PrLD mutations that abolish phase separation (such as the removal of aromatic residues) also prevent biofilm formation. Biofilm TF condensates can selectively recruit other TFs through PrLD-PrLD interactions and can co-recruit RNA polymerase II, implicating condensate formation in the assembly of active transcriptional complexes. Finally, we show that PrLD mutations that block the phase separation of biofilm TFs also prevent filamentation in an in vivo model of gastrointestinal colonization. Together, these studies associate transcriptional condensates with the regulation of filamentation and biofilm formation in C. albicans, and highlight how targeting of PrLD-PrLD interactions could prevent pathogenesis by this species.

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Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains.

Project description:Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well characterized, but little is known about the mechanisms by which ADs effect gene activation. Here, we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation.

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Transcription factors activate genes through the phase separation capacity of their activation domains

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-10-26 | GSE120476 | GEO