Title

H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine

Date

11-11-2008

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Elucidating how chromatin influences gene expression patterns and ultimately cell fate is fundamental to understanding development and disease. The histone variant H2AZ has emerged as a key regulator of chromatin function and plays an essential but unknown role during mammalian development. Here, genome-wide analysis reveals that H2AZ occupies the promoters of developmentally important genes in a manner that is remarkably similar to that of the Polycomb group (PcG) protein Suz12. By using RNAi, we demonstrate a role for H2AZ in regulating target gene expression, find that H2AZ and PcG protein occupancy is interdependent at promoters, and further show that H2AZ is necessary for ES cell differentiation. Notably, H2AZ occupies a different subset of genes in lineage-committed cells, suggesting that its dynamic redistribution is necessary for cell fate transitions. Thus, H2AZ, together with PcG proteins, may establish specialized chromatin states in ES cells necessary for the proper execution of developmental gene expression programs.

Rights and Permissions

Citation: Cell. 2008 Nov 14;135(4):649-61. Epub 2008 Nov 6. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

18992931