Journalartikel

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


AutorenlistePünzeler, S; Link, S; Wagner, G; Keilhauer, EC; Kronbeck, N; Spitzer, RMM; Leidescher, S; Markaki, Y; Mentele, E; Regnard, C; Schneider, K; Takahashi, D; Kusakabe, M; Vardabasso, C; Zink, LM; Bernstein, E; Straub, T; Leonhardt, H; Harata, M; Rupp, R; Mann, M; Hake, SB

Jahr der Veröffentlichung2017

Seiten2263-2279

ZeitschriftThe EMBO Journal

Bandnummer36

Heftnummer15

ISSN1460-2075

Open Access StatusGreen

DOI Linkhttps://doi.org/10.15252/embj.201695757

VerlagEMBO Press


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.



Autoren/Herausgeber




Zitierstile

Harvard-ZitierstilPünzeler, S., Link, S., Wagner, G., Keilhauer, E., Kronbeck, N., Spitzer, R., et al. (2017) Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation, The EMBO Journal, 36(15), pp. 2263-2279. https://doi.org/10.15252/embj.201695757

APA-ZitierstilPünzeler, S., Link, S., Wagner, G., Keilhauer, E., Kronbeck, N., Spitzer, R., Leidescher, S., Markaki, Y., Mentele, E., Regnard, C., Schneider, K., Takahashi, D., Kusakabe, M., Vardabasso, C., Zink, L., Bernstein, E., Straub, T., Leonhardt, H., Harata, M., ...Hake, S. (2017). Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation. The EMBO Journal. 36(15), 2263-2279. https://doi.org/10.15252/embj.201695757



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