This article is part of a special issue on epigenomics.

Open Access Open Badges Research

H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions

Manching Ku1234*, Jacob D Jaffe3, Richard P Koche12345, Esther Rheinbay12346, Mitsuhiro Endoh7, Haruhiko Koseki7, Steven A Carr3 and Bradley E Bernstein1234*

Author Affiliations

1 Department of Pathology, Center for Systems Biology and Center for Cancer Research, Massachusetts General Hospital, Simches Research Building, CPZN 8234, Boston, MA 02114, USA

2 Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815-6789, USA

3 Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA

4 Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA

5 Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E25-519, Cambridge, MA 02139, USA

6 Bioinformatics Program and Department of Biomedical Engineering, Boston University, 24 Cummington Street, Boston, MA 02215, USA

7 RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan

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Genome Biology 2012, 13:R85  doi:10.1186/gb-2012-13-10-r85

Published: 3 October 2012



The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure.


We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin.


Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles.

Acetylation; bivalent; ChIP-Seq; H2A.Z; mass spectrometry; ubiquitination