Format

Send to

Choose Destination
Nat Neurosci. 2016 Oct;19(10):1321-30. doi: 10.1038/nn.4360. Epub 2016 Aug 15.

Polycomb repressive complex 2 (PRC2) silences genes responsible for neurodegeneration.

Author information

1
Friedman Brain Institute, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
2
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
3
BD2K-LINCS Data Coordination and Integration Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
4
Genomics Resource Center, The Rockefeller University, New York, New York, USA.
5
Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, New York, USA.

Abstract

Normal brain function depends on the interaction between highly specialized neurons that operate within anatomically and functionally distinct brain regions. Neuronal specification is driven by transcriptional programs that are established during early neuronal development and remain in place in the adult brain. The fidelity of neuronal specification depends on the robustness of the transcriptional program that supports the neuron type-specific gene expression patterns. Here we show that polycomb repressive complex 2 (PRC2), which supports neuron specification during differentiation, contributes to the suppression of a transcriptional program that is detrimental to adult neuron function and survival. We show that PRC2 deficiency in striatal neurons leads to the de-repression of selected, predominantly bivalent PRC2 target genes that are dominated by self-regulating transcription factors normally suppressed in these neurons. The transcriptional changes in PRC2-deficient neurons lead to progressive and fatal neurodegeneration in mice. Our results point to a key role of PRC2 in protecting neurons against degeneration.

PMID:
27526204
PMCID:
PMC5088783
DOI:
10.1038/nn.4360
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center