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

TY - JOUR

T1 - Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation

AU - Pünzeler, Sebastian

AU - Link, Stephanie

AU - Wagner, Gabriele

AU - Keilhauer, Eva C

AU - Kronbeck, Nina

AU - Spitzer, Ramona Mm

AU - Leidescher, Susanne

AU - Markaki, Yolanda

AU - Mentele, Edith

AU - Regnard, Catherine

AU - Schneider, Katrin

AU - Takahashi, Daisuke

AU - Kusakabe, Masayuki

AU - Vardabasso, Chiara

AU - Zink, Lisa M

AU - Straub, Tobias

AU - Bernstein, Emily

AU - Harata, Masahiko

AU - Leonhardt, Heinrich

AU - Mann, Matthias

AU - Rupp, Ralph Aw

AU - Hake, Sandra B

N1 - © 2017 The Authors.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line

KW - Chromatin

KW - Chromosomal Proteins, Non-Histone

KW - Gene Expression Regulation

KW - Histones

KW - Humans

KW - Mitosis

KW - Neural Crest

KW - Protein Binding

KW - Xenopus

KW - Journal Article

U2 - 10.15252/embj.201695757

DO - 10.15252/embj.201695757

M3 - Journal article

C2 - 28645917

SN - 0261-4189

VL - 36

SP - 2263

EP - 2279

JO - E M B O Journal

JF - E M B O Journal

IS - 15

ER -