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Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression (ChIP-Seq)

ABSTRACT: Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression (ChIP-Seq)

PROVIDER: PRJNA1060323 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27400127_1.fastq.gz	Fastqsanger.gz
	SRR27400127_2.fastq.gz	Fastqsanger.gz
	SRR27400128_1.fastq.gz	Fastqsanger.gz
	SRR27400128_2.fastq.gz	Fastqsanger.gz
	SRR27400129_1.fastq.gz	Fastqsanger.gz

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Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression

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Project description:Some transcription factors (TFs) can form liquid-liquid phase separated (LLPS) condensates. However, the function of these TF condensates in 3D genome organization and gene regulation remains elusive. In response to methionine (met) starvation in budding yeast, Met4 and a few sequence-specific co-activators, including Met32, induce a set of genes involved in met biosynthesis. Here, we show that the endogenous Met4 and Met32 form puncta-like structures that significantly overlap in yeast nuclei upon met depletion. Recombinant Met4 and Met32 form mixed droplets with LLPS properties in vitro. In relation to chromatin, Met4 puncta co-localize with target genes, and at least a subset of these target genes are clustered in 3D in a Met4-dependent manner. A MET3pr-GFP reporter inserted near several native Met4 binding sites becomes co-localized with Met4 puncta and displays enhanced transcriptional activity. A Met4 variant with a partial truncation of an intrinsically disordered region (IDR) shows less puncta formation, and this mutant selectively reduces the reporter activity near Met4 binding sites to the basal level. Overall, these results support a model where Met4 and co-activators form condensates to bring multiple target genes into a vicinity with higher local TF concentrations, which facilitates a strong response to met depletion (-met).

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Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression (RNA-Seq)

Project description:Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression (RNA-Seq)

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Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression (RNA-Seq)

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Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression (ChIP-Seq)

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Transcription Factor Condensates Mediate Clustering of <i>MET</i> Regulon and Enhancement in Gene Expression.

Project description: Not available

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Transcription Factor Condensates Mediate Clustering of MET Regulon and Enhancement in Gene Expression

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

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Transcription factor condensates, 3D clustering, and gene expression enhancement of the <i>MET</i> regulon.

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SGF29 nuclear condensates mediate cellular aging

Project description:Phase separation, a biophysical segregation of subcellular milieus referred as condensates, is known to regulate transcription but its impacts on physiological processes are less clear. Here, we asked how the candidate phase regulator SGF29, a component of the transcriptional coactivator complex SAGA, regulates transcriptional events in aging. We 36 demonstrate that SGF29 forms liquid-like nuclear condensates as human mesenchymal 37 progenitor cells (hMPCs) become senescent. Mechanistically, SGF29 partitions with the 38 transcription factor SP1, RNA polymerase II and the transcriptional coactivator MED4 to form transcriptionally active condensates. These then target specific genomic loci, such as the CDKN1A promoter, to drive senescence-related gene expression. The Arg 207 in the intrinsically disordered region is identified as the key amino acid residue for SGF29 to form phase separation and activate CDKN1A transcription. Our study links phase separation to aging regulation and reveals nuclear condensates as a functional unit shaping transcriptional landscapes in aging.

2023-02-24 | PXD040372 |

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