Ezh1 (a member of Polycomb Repressive Complex 2) associated transcription in the hippocampus

Saez, Mauricio; Sanchez , Mario; van Zundert, Brigitte; Montecino, Martin

Abstract

Methylation of lysine 27 of histone H3 (H3K27me3) is an epigenetic mark that has been principally associated with gene silencing during cell differentiation. This methylation is mediated by the Polycomb Repressive Complex 2 (PRC2) which contains two catalytic subunits, Ezh1 and Ezh2. Ezh1 has been shown as the main isoform in PRC2 in post-mitotic cells, exhibiting lower enzymatic efficiency than Ezh2-containing complexes. In recent years, Ezh1 has been also found associated with transcriptionally active gene promoters in several cell types. Here, we have analysed global profiles of H3K27me3 and H3K27Ac enrichments using publicly-available ChIP-seq data (http://www.ncbi.nlm.nih.gov/gds) from mouse hippocampal tissue. Additionally, using ChIP-seq we determined the genomic distribution of Ezh1 in hippocampal cells as well as in FACS-purified hippocampal neural nuclei. The data were clustered according to the expression profiles of putative targets obtained from transcriptomic analyses and aligned with respect to the H3K27me3/H3K27ac enrichment levels. Our results indicate that in hippocampal cells Ezh1 is significantly enriched at transcriptionally active gene promoters and enhancers and poorly associated with H3K27me3-marked transcriptionally inactive genomic regions. Together, our results provide a new layer of complexity among the epigenetic mechanisms that control genes associated with hippocampal neuron function. We propose that PRC2-Ezh1 contributes to the transcriptional activity of a significant group of neural genes by interacting, together with the transcriptional machinery, with their promoters and enhancers.

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Año de Inicio/Término: 5 al 9 de Noviembre