Genomics

Dataset Information

302

AUTS2 confers transcriptional activation to PRC1 in the CNS (ChIP-Seq)


ABSTRACT: Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. ChIP-seq experiments of PRC1 components, PolII as well as histone modifications were performed either in mouse whole brain or in human 293T-REx lines expressing FLAG/HA-tagged subunits. RNA-seq was performed to analyze the expression profile of mouse whole brain.

ORGANISM(S): Musculus  

SUBMITTER: Zhonghua Gao   Pedro Lee  Danny Reinberg  Melanie von Schimmelmann  Anne Schaefer  James M Stafford 

PROVIDER: E-GEOD-60409 | ArrayExpress | 2014-12-18

SECONDARY ACCESSION(S): GSE60409SRP045494PRJNA258289

REPOSITORIES: GEO, ArrayExpress, ENA

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