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Laue, K.* ; Daujat, S.* ; Crump, J.G.* ; Plaster, N.* ; Roehl, H.H.* ; Kimmel, C.B.* ; Schneider, R.* ; Hammerschmidt, M.*

The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity.

Development 135, 1935-1946 (2008)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The Trithorax group (TrxG) is composed of diverse, evolutionary conserved proteins that form chromatin-associated complexes accounting for epigenetic transcriptional memory. However, the molecular mechanisms by which particular loci are marked for reactivation after mitosis are only partially understood. Here, based on genetic analyses in zebrafish, we identify the multidomain protein Brpf1 as a novel TrxG member with a central role during development. brpf1 mutants display anterior transformations of pharyngeal arches due to progressive loss of anterior Hox gene expression. Brpf1 functions in association with the histone acetyltransferase Moz (Myst3), an interaction mediated by the N-terminal domain of Brpf1, and promotes histone acetylation in vivo. Brpf1 recruits Moz to distinct sites of active chromatin and remains at chromosomes during mitosis, mediated by direct histone binding of its bromodomain, which has a preference for acetylated histones, and its PWWP domain, which binds histones independently of their acetylation status. This is the first demonstration of histone binding for PWWP domains. Mutant analyses further show that the PWWP domain is absolutely essential for Brpf1 function in vivo. We conclude that Brpf1, coordinated by its particular set of domains, acts by multiple mechanisms to mediate Moz-dependent histone acetylation and to mark Hox genes for maintained expression throughout vertebrate development.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2008
HGF-reported in Year 0
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Quellenangaben Volume: 135, Issue: 11, Pages: 1935-1946 Article Number: , Supplement: ,
Publisher Company of Biologists
Reviewing status Peer reviewed
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502800-001
PubMed ID 18469222
Erfassungsdatum 2008-12-31