Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation
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Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation. / Pünzeler, Sebastian; Link, Stephanie; Wagner, Gabriele; Keilhauer, Eva C; Kronbeck, Nina; Spitzer, Ramona Mm; Leidescher, Susanne; Markaki, Yolanda; Mentele, Edith; Regnard, Catherine; Schneider, Katrin; Takahashi, Daisuke; Kusakabe, Masayuki; Vardabasso, Chiara; Zink, Lisa M; Straub, Tobias; Bernstein, Emily; Harata, Masahiko; Leonhardt, Heinrich; Mann, Matthias; Rupp, Ralph Aw; Hake, Sandra B.
In: E M B O Journal, Vol. 36, No. 15, 01.08.2017, p. 2263-2279.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 36
SP - 2263
EP - 2279
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 15
ER -
ID: 184291999