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

Sebastian Pünzeler, Stephanie Link, Gabriele Wagner, Eva C. Keilhauer, Nina Kronbeck, Ramona M.M. Spitzer, Susanne Leidescher, Yolanda Markaki, Edith Mentele, Catherine Regnard, Katrin Schneider, Daisuke Takahashi, Masayuki Kusakabe, Chiara Vardabasso, Lisa M. Zink, Tobias Straub, Emily Bernstein, Masahiko Harata, Heinrich Leonhardt, Matthias MannRalph A.W. Rupp, Sandra B. Hake

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2263-2279
Number of pages17
JournalEMBO Journal
Volume36
Issue number15
DOIs
Publication statusPublished - 2017 Aug 1

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation'. Together they form a unique fingerprint.

Cite this