QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online May 9, 2008
doi: 10.1242/10.1242/dev.017160

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laue, K. Articles by Hammerschmidt, M. Search for Related Content PubMed PubMed Citation Articles by Laue, K. Articles by Hammerschmidt, M. Social Bookmarking                         What's this?

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

Kathrin Laue^1,*, Sylvain Daujat^2,*, Justin Gage Crump³, Nikki Plaster^1,, Henry H. Roehl⁴ Tübingen 2000 Screen Consortium, Charles B. Kimmel⁵, Robert Schneider^2,, Matthias Hammerschmidt^1,6,

¹ Georges-Koehler-Laboratory and
² Hans-Spemann-Laboratory, Max-Planck-Institute of Immunobiology, Stuebeweg 51, D-79108 Freiburg, Germany.
³ Center for Stem Cell and Regenerative Medicine, USC Keck School of Medicine, Los Angeles, CA 90033, USA.
⁴ Centre of Developmental and Biomedical Genetics, University of Sheffield, Sheffield S10 2TN, UK.
⁵ Institute of Neuroscience, 1254 University of Oregon, Eugene, OR, USA.
⁶ Institute for Developmental Biology, University of Cologne, D-50923 Cologne, Germany.

Author for correspondence (e-mail: schneiderr{at}immunbio.mpg.de)

Alternate author for correspondence (e-mail: hammerschmid{at}immunbio.mpg.de)

Accepted 27 March 2008

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.

Key words: Brpf1, Bromodomain, PWWP domain, Moz, Hox gene expression, Craniofacial development, Cranial neural crest, Pharyngeal arch, Anterior-posterior patterning, Homeotic transformation, Zebrafish

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M.-C. Shun, Y. Botbol, X. Li, F. Di Nunzio, J. E. Daigle, N. Yan, J. Lieberman, M. Lavigne, and A. Engelman Identification and Characterization of PWWP Domain Residues Critical for LEDGF/p75 Chromatin Binding and Human Immunodeficiency Virus Type 1 Infectivity J. Virol., December 1, 2008; 82(23): 11555 - 11567. [Abstract] [Full Text] [PDF]

				M. Ullah, N. Pelletier, L. Xiao, S. P. Zhao, K. Wang, C. Degerny, S. Tahmasebi, C. Cayrou, Y. Doyon, S.-L. Goh, et al. Molecular Architecture of Quartet MOZ/MORF Histone Acetyltransferase Complexes Mol. Cell. Biol., November 15, 2008; 28(22): 6828 - 6843. [Abstract] [Full Text] [PDF]

				K. Laue, M. Janicke, N. Plaster, C. Sonntag, and M. Hammerschmidt Restriction of retinoic acid activity by Cyp26b1 is required for proper timing and patterning of osteogenesis during zebrafish development Development, November 15, 2008; 135(22): 3775 - 3787. [Abstract] [Full Text] [PDF]