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Intrinsically disordered regions of transcription factor encode multiple functions using interwoven sequence grammars (ChEC-seq)

ABSTRACT: Intrinsically disordered regions of transcription factor encode multiple functions using interwoven sequence grammars (ChEC-seq)

PROVIDER: PRJNA1001336 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25493300_1.fastq.gz	Fastqsanger.gz
	SRR25493300_2.fastq.gz	Fastqsanger.gz
	SRR25493301_1.fastq.gz	Fastqsanger.gz
	SRR25493301_2.fastq.gz	Fastqsanger.gz
	SRR25493302_1.fastq.gz	Fastqsanger.gz

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Intrinsically disordered regions of transcription factor encode multiple functions using interwoven sequence grammars (ChEC-seq)

Project description:Intrinsically disordered regions (IDRs) are abundant within eukaryotic proteins, but their sequence-function relationship remains poorly understood. IDRs of transcription factors (TFs) can direct promoter selection and recruit coactivators, as exemplified by the budding-yeast TF- Msn2. To examine how low-complexity IDRs encode multiple functions, we compared genomic binding preferences, gene induction, and coactivator recruitment amongst a large set of designed Mns2-IDR mutants. We show that multiple regions across the >500AA IDR contribute to both functions. Yet, transcription activity was readily disrupted by variants having no consequences on Msn2 binding. Our data attribute this differential sensitivity to the integration of relaxed, composition-based code directing binding preferences with a more stringent, motif-based code controlling the recruitment of coactivators and transcription activity. Interwoven sequence grammar may present a general paradigm through which low-complexity IDRs encode multiple functions.

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Intrinsically disordered regions of the Msn2 transcription factor encode multiple functions using interwoven sequence grammars

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Intrinsically disordered regions of transcription factor encode multiple functions using interwoven sequence grammars (RNA-Seq)

Project description:Intrinsically disordered regions of transcription factor encode multiple functions using interwoven sequence grammars (RNA-Seq)

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Intrinsically disordered regions regulate RhlE RNA helicase functions in bacteria

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BRCA1/BARD1 intrinsically disordered regions facilitate chromatin recruitment and ubiquitylation

Project description:BRCA1/BARD1 is a tumor suppressor E3 ubiquitin (Ub) ligase with roles in DNA damage repair and in transcriptional regulation. BRCA1/BARD1 RING domains interact with nucleosomes to facilitate mono-ubiquitylation of distinct residues on the C-terminal tail of histone H2A. These enzymatic domains constitute a small fraction of the heterodimer, raising the possibility of functional chromatin interactions involving other regions such as the BARD1 C-terminal domains that bind nucleosomes containing the DNA damage signal H2A K15-Ub and H4 K20me0, or portions of the expansive intrinsically disordered regions found in both subunits. Herein, we reveal novel interactions that support robust H2A ubiquitylation activity mediated through a high-affinity, intrinsically disordered DNA-binding region of BARD1. These interactions support BRCA1/BARD1 recruitment to chromatin and sites of DNA damage in cells and contribute to their survival. We also reveal distinct BRCA1/BARD1 complexes that depend on the presence of H2A K15-Ub, including a complex where a single BARD1 subunit spans adjacent nucleosome units. Our findings identify an extensive network of multivalent BARD1-nucleosome interactions that serve as a platform for BRCA1/BARD1-associated functions on chromatin.

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