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 PMID:25519132  

An AUTS2-Polycomb complex activates gene expression in the CNS.

Zhonghua Gao | Pedro Lee | James M Stafford | Melanie von Schimmelmann | Anne Schaefer | Danny Reinberg
Nature | 2014

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). Although AUTS2 is often disrupted in patients with neuronal disorders, the mechanism underlying the pathogenesis 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 neutralizes PRC1 repressive activity, whereas AUTS2-mediated recruitment of P300 leads to gene activation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2 in the mouse central nervous system (CNS) leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.

Pubmed ID: 25519132

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA016087
  • Agency: NCI NIH HHS, United States
    Id: 5T32CA160002
  • Agency: NIMH NIH HHS, United States
    Id: DP2 MH100012
  • Agency: NIGMS NIH HHS, United States
    Id: GM-64844
  • Agency: NIGMS NIH HHS, United States
    Id: 1F32GM105275
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM064844
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIAAA NIH HHS, United States
    Id: F32AA022842
  • Agency: NCCDPHP CDC HHS, United States
    Id: 1DP2MH100012-01
  • Agency: NCI NIH HHS, United States
    Id: T32 CA160002
  • Agency: NIAAA NIH HHS, United States
    Id: F32 AA022842
  • Agency: NIGMS NIH HHS, United States
    Id: F32 GM105275

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RRID:SCR_005012

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