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BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae (ChIP-Seq)

ABSTRACT: BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae (ChIP-Seq)

PROVIDER: PRJNA718273 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14094800_1.fastq.gz	Fastqsanger.gz
	SRR14094800_2.fastq.gz	Fastqsanger.gz
	SRR14094801_1.fastq.gz	Fastqsanger.gz
	SRR14094801_2.fastq.gz	Fastqsanger.gz
	SRR14094802_1.fastq.gz	Fastqsanger.gz

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BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae (ChIP-Seq)

Project description:Human BET family members are promising targets in the therapy of cancer and immunoinflammatory diseases, but their mechanism of action and functional redundancies are poorly understood. Yeast BET factors Bdf1/2 were previously proposed to act as anchors for coactivator TFIID. We investigated their genome wide roles in transcription and found that, while they cooperate with TFIID at many genes, their contributions to transcription are often significantly different. Bdf1/2 co-occupy the majority of yeast promoters and affect preinitiation complex formation by participating in recruitment of TFIID, Mediator and basal factors to chromatin. Surprisingly, we discovered that hypersensitivity of genes to Bdf1/2 depletion results from combined defects in initiation of transcription and early elongation. Bdf1/2 are critical components of yeast transcriptional machinery with many functional similarities to human BET proteins, most notably Brd4.

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BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae

Project description:BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae

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Project description:BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae (RNA-Seq)

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BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae.

Project description:Human bromodomain and extra-terminal domain (BET) family members are promising targets for therapy of cancer and immunoinflammatory diseases, but their mechanisms of action and functional redundancies are poorly understood. Bdf1/2, yeast homologues of the human BET factors, were previously proposed to target transcription factor TFIID to acetylated histone H4, analogous to bromodomains that are present within the largest subunit of metazoan TFIID. We investigated the genome-wide roles of Bdf1/2 and found that their important contributions to transcription extend beyond TFIID function as transcription of many genes is more sensitive to Bdf1/2 than to TFIID depletion. Bdf1/2 co-occupy the majority of yeast promoters and affect preinitiation complex formation through recruitment of TFIID, Mediator, and basal transcription factors to chromatin. Surprisingly, we discovered that hypersensitivity of genes to Bdf1/2 depletion results from combined defects in transcription initiation and early elongation, a striking functional similarity to human BET proteins, most notably Brd4. Our results establish Bdf1/2 as critical for yeast transcription and provide important mechanistic insights into the function of BET proteins in all eukaryotes.

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BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae

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

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Project description:Bromodomain and Extra-terminal motif (BET) proteins play a central role in transcription regulation and chromatin signalling pathways. In yeast, Bdf1 and its homologous protein Bdf2 are partially redundant and the deletion of both genes is lethal. Most of Bdf1 functions have been investigated in vegetative cells even if this protein is essential for sporulation. In this study, we explored for the first time the functional role of the Bdf1 bromodomains during the sporulation program. Extensive purification of Bdf1 partners identified two independent complexes with Bdf2 or the Swr1 complex. However, none of them are required for meiotic gene regulation or to complete sporulation. Taken together, our results unveil a new role for Bdf1 as a meiotic-specific gene transcriptional regulator independently of its predominant protein partners.

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Project description:Bromodomain and extraterminal proteins (BET) are epigenetic adaptors that play critical roles in gene regulation. This protein family contains two conserved bromodomains which can mediate the interaction with acetylated histone lysine residues and/or other acetylated proteins, and one extraterminal (ET) domain. BET protein inhibition has been recognized as a promising therapeutic strategy for several diseases, including acute myeloid leukaemia, castration resistant prostate cancer, and triple negative breast cancer. BET inhibition by a specific inhibitor JQ1 caused an impairment in various brain functions but the underlying molecular mechanisms are not well understood. Among BET family members, BRD4 has been recognized for its prominent role in epigenetic regulation of gene expression. However, we have found an extensive functional redundancy and coordination among all three major BET family members (BRD2/3/4) during the activity-dependent gene induction in neurons, which is also reflected in learning and memory behavior. Our study further revealed the molecular hierarchy in the coordination of BET family proteins dissecting their distinctive functions during gene induction required for proper brain function and plasticity. Understanding the functional coordination of BET family proteins at the molecular level would be beneficial to the development of more selective interventions for various diseases that are caused by dysregulated epigenetic pathways.

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