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

105 Citations (Scopus)

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

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Polycomb Repressive Complex 1
Autistic Disorder
Central Nervous System
Gene Expression
Polycomb-Group Proteins
Chromatin Immunoprecipitation
Epigenomics
Transcriptional Activation

All Science Journal Classification (ASJC) codes

  • General

Cite this

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
Gao, Zhonghua ; Lee, Pedro ; Stafford, James M. ; Schimmelmann, Melanie Von ; Schaefer, Anne ; Reinberg, Danny. / An AUTS2-Polycomb complex activates gene expression in the CNS. In: Nature. 2014 ; Vol. 516, No. 7531. pp. 349-354.
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Gao, Z, Lee, P, Stafford, JM, Schimmelmann, MV, Schaefer, A & Reinberg, D 2014, 'An AUTS2-Polycomb complex activates gene expression in the CNS', Nature, vol. 516, no. 7531, pp. 349-354. https://doi.org/10.1038/nature13921

An AUTS2-Polycomb complex activates gene expression in the CNS. / Gao, Zhonghua; Lee, Pedro; Stafford, James M.; Schimmelmann, Melanie Von; Schaefer, Anne; Reinberg, Danny.

In: Nature, Vol. 516, No. 7531, 18.12.2014, p. 349-354.

Research output: Contribution to journalArticle

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Gao Z, Lee P, Stafford JM, Schimmelmann MV, Schaefer A, Reinberg D. An AUTS2-Polycomb complex activates gene expression in the CNS. Nature. 2014 Dec 18;516(7531):349-354. https://doi.org/10.1038/nature13921