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EMBO J. 2017 Aug 1;36(15):2263-2279. doi: 10.15252/embj.201695757. Epub 2017 Jun 23.

Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation.

Author information

1
Department of Molecular Biology, BioMedical Center (BMC), Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
2
Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
3
Department of Biology, Biozentrum, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
4
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Aoba-ku Sendai, Japan.
5
Department of Oncological Sciences and Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Center for Integrated Protein Science Munich (CIPSM), Munich, Germany.
7
Department of Molecular Biology, BioMedical Center (BMC), Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany sandra.hake@gen.bio.uni-giessen.de.

Abstract

Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain exhibits direct DNA binding. Genome-wide mapping reveals that PWWP2A binds selectively to H2A.Z-containing nucleosomes with strong preference for promoters of highly transcribed genes. In human cells, its depletion affects gene expression and impairs proliferation via a mitotic delay. While PWWP2A does not influence H2A.Z occupancy, the C-terminal tail of H2A.Z is one important mediator to recruit PWWP2A to chromatin. Knockdown of PWWP2A in Xenopus results in severe cranial facial defects, arising from neural crest cell differentiation and migration problems. Thus, PWWP2A is a novel H2A.Z-specific multivalent chromatin binder providing a surprising link between H2A.Z, chromosome segregation, and organ development.

KEYWORDS:

H2A.Z; PWWP2A; chromatin; mitosis; neural crest

PMID:
28645917
PMCID:
PMC5538766
DOI:
10.15252/embj.201695757
[Indexed for MEDLINE]
Free PMC Article

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