An AUTS2-Polycomb complex activates gene expression in the CNS

Zhonghua Gao, Pedro Lee, James M. Stafford, Melanie Von Schimmelmann, Anne Schaefer, Danny Reinberg

Research output: Contribution to journalArticle

111 Scopus citations

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). Although AUTS2 is often disrupted in patients withneuronal disorders, themechanism underlying the pathogenesis is unclear.Weinvestigated the role ofAUTS2 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.

Original languageEnglish (US)
Pages (from-to)349-354
Number of pages6
JournalNature
Volume516
Issue number7531
DOIs
StatePublished - Dec 18 2014

All Science Journal Classification (ASJC) codes

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    Gao, Z., Lee, P., Stafford, J. M., Schimmelmann, M. V., Schaefer, A., & Reinberg, D. (2014). An AUTS2-Polycomb complex activates gene expression in the CNS. Nature, 516(7531), 349-354. https://doi.org/10.1038/nature13921