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

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

PROVIDER: PRJNA1001333 | ENA |

REPOSITORIES: ENA

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

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

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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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