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H2A.Z nucleosomes enriched over active genes are homotypic

Nature Structural & Molecular Biology volume 17, pages 1500–1507 (2010)Cite this article

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Abstract

Nucleosomes that contain the histone variant H2A.Z are enriched around transcriptional start sites, but the mechanistic basis for this enrichment is unknown. A single octameric nucleosome can contain two H2A.Z histones (homotypic) or one H2A.Z and one canonical H2A (heterotypic). To elucidate the function of H2A.Z, we generated high-resolution maps of homotypic and heterotypic Drosophila H2A.Z (H2Av) nucleosomes. Although homotypic and heterotypic H2A.Z nucleosomes mapped throughout most of the genome, homotypic nucleosomes were enriched and heterotypic nucleosomes were depleted downstream of active promoters and intron-exon junctions. The distribution of homotypic H2A.Z nucleosomes resembled that of classical active chromatin and showed evidence of disruption during transcriptional elongation. Both homotypic H2A.Z nucleosomes and classical active chromatin were depleted downstream of paused polymerases. Our results suggest that H2A.Z enrichment patterns result from intrinsic structural differences between heterotypic and homotypic H2A.Z nucleosomes that follow disruption during transcriptional elongation.

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Figure 1: Broad distribution of homotypic and heterotypic H2Av nucleosomes.
Figure 2: Homotypic H2Av nucleosomes are enriched downstream of gene promoters.
Figure 3: Homotypic H2Av nucleosomes are enriched downstream of intron-exon junctions and are low-salt soluble.
Figure 4: Depletion of homotypic H2Av nucleosomes at genes with stalled Pol II.
Figure 5: Low-salt extracted chromatin reveals distinctive features of RNA Pol II stalling.
Figure 6: Model for the generation of H2A.Z enrichment patterns.

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Acknowledgements

We thank F. Loos for participating in early stages of this study, A. Marty (Hutchinson Center Shared Genomics Resource) for Illumina sequencing, E. Greene for help with Solexa analysis, R. Glaser (Wadsworth Center, New York State Department of Health) for the H2Av antibody and M. Conerly, R. Deal, P. Talbert and E. Wolff for comments. This work was supported by the Howard Hughes Medical Institute.

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  1. Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Christopher M Weber, Jorja G Henikoff & Steven Henikoff

  2. Molecular and Cellular Biology Program, University of Washington, Seattle, Washington, USA

    Christopher M Weber

  3. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Steven Henikoff

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C.M.W. performed the experiments, J.G.H. did the analysis, S.H. supervised the work and C.M.W. and S.H. wrote the paper.

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Correspondence to Steven Henikoff.

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Weber, C., Henikoff, J. & Henikoff, S. H2A.Z nucleosomes enriched over active genes are homotypic. Nat Struct Mol Biol 17, 1500–1507 (2010). https://doi.org/10.1038/nsmb.1926

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