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E-GEOD-60410 - AUTS2 confers transcriptional activation to PRC1 in the CNS (RNA-Seq)

Status
Released on 18 December 2014, last updated on 2 January 2015
Organism
Mus musculus
Samples (1)
Protocols (1)
Description
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). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism 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 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. mRNA profiles of P1 brain from wild type mice were generated by deep sequencing
Experiment type
RNA-seq of coding RNA 
Contacts
Anne Schaefer, Danny Reinberg, James M Stafford, Melanie von Schimmelmann, Pedro Lee, Zhonghua Gao
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-60410.idf.txt
Sample and data relationshipE-GEOD-60410.sdrf.txt
Processed data (1)E-GEOD-60410.processed.1.zip
Links