An AUTS2–Polycomb complex activates gene expression in the CNS

Zhonghua Gao, Pedro Lee, James M. Stafford, Melanie von Schimmelmann, Anne Schaefer and Danny Reinberg ()
Additional contact information
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

Nature, 2014, vol. 516, issue 7531, 349-354

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/nature13921 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:516:y:2014:i:7531:d:10.1038_nature13921

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature13921

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().