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

Fiche publication


Date publication

juin 2008

Journal

Development (Cambridge, England)

Auteurs

Membres identifiés du Cancéropôle Est :
Dr DAUJAT Sylvain


Tous les auteurs :
Laue K, Daujat S, Crump JG, Plaster N, Roehl HH, , Kimmel CB, Schneider R, Hammerschmidt M

Résumé

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.

Mots clés

Acetylation, Animals, Binding Sites, genetics, Branchial Region, anatomy & histology, Carrier Proteins, genetics, Cell Line, Chromatin, metabolism, Gene Expression Regulation, Developmental, Histone Acetyltransferases, genetics, Histones, metabolism, Humans, Immunoprecipitation, In Situ Hybridization, Mice, Nuclear Proteins, genetics, Protein Binding, Recombinant Proteins, metabolism, Zebrafish, genetics, Zebrafish Proteins, genetics

Référence

Development. 2008 Jun;135(11):1935-46