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An AUTS2–Polycomb complex activates gene expression in the CNS

Author

Listed:
  • Zhonghua Gao

    (Howard Hughes Medical Institute, New York University Langone School of Medicine)

  • Pedro Lee

    (Howard Hughes Medical Institute, New York University Langone School of Medicine)

  • James M. Stafford

    (Howard Hughes Medical Institute, New York University Langone School of Medicine)

  • Melanie von Schimmelmann

    (Friedman Brain Institute, Mount Sinai School of Medicine)

  • Anne Schaefer

    (Friedman Brain Institute, Mount Sinai School of Medicine)

  • Danny Reinberg

    (Howard Hughes Medical Institute, New York University Langone School of Medicine)

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 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.

Suggested Citation

  • Zhonghua Gao & Pedro Lee & James M. Stafford & Melanie von Schimmelmann & Anne Schaefer & Danny Reinberg, 2014. "An AUTS2–Polycomb complex activates gene expression in the CNS," Nature, Nature, vol. 516(7531), pages 349-354, December.
    • Handle: RePEc:nat:nature:v:516:y:2014:i:7531:d:10.1038_nature13921
    DOI: 10.1038/nature13921
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    Cited by:

    1. Beatriz del Blanco & Sergio Niñerola & Ana M. Martín-González & Juan Paraíso-Luna & Minji Kim & Rafael Muñoz-Viana & Carina Racovac & Jose V. Sanchez-Mut & Yijun Ruan & Ángel Barco, 2024. "Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Takeo Kubota & Kazuki Mochizuki, 2016. "Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders," IJERPH, MDPI, vol. 13(5), pages 1-12, May.
    3. Xianchun Lan & Song Ding & Tianzhe Zhang & Ying Yi & Conghui Li & Wenwen Jin & Jian Chen & Kaiwei Liang & Hengbin Wang & Wei Jiang, 2022. "PCGF6 controls neuroectoderm specification of human pluripotent stem cells by activating SOX2 expression," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Lihu Gong & Xiuli Liu & Lianying Jiao & Xin Yang & Andrew Lemoff & Xin Liu, 2022. "CK2-mediated phosphorylation of SUZ12 promotes PRC2 function by stabilizing enzyme active site," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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