| First Author | Gao Z | Year | 2014 |
| Journal | Nature | Volume | 516 |
| Issue | 7531 | Pages | 349-54 |
| PubMed ID | 25519132 | Mgi Jnum | J:217675 |
| Mgi Id | MGI:5615311 | Doi | 10.1038/nature13921 |
| Citation | Gao Z, et al. (2014) An AUTS2-Polycomb complex activates gene expression in the CNS. Nature 516(7531):349-54 |
| abstractText | 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. |
