PUBLICATION
The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity
- Authors
- Laue, K., Daujat, S., Crump, J.G., Plaster, N., Roehl, H.H., Tübingen 2000 Screen Consortium, Kimmel, C.B., Schneider, R., and Hammerschmidt, M.
- ID
- ZDB-PUB-080515-4
- Date
- 2008
- Source
- Development (Cambridge, England) 135(11): 1935-1946 (Journal)
- Registered Authors
- Crump, Gage DeKoeyer, Hammerschmidt, Matthias, Kimmel, Charles B., Laue, Kathrin, Plaster, Nikki, Roehl, Henry
- Keywords
- Brpf1, Bromodomain, PWWP domain, Moz, Hox gene expression, Craniofacial development, Cranial neural crest, Pharyngeal arch, Anterior-posterior patterning, Homeotic transformation, Zebrafish
- MeSH Terms
-
- Acetylation
- Animals
- Binding Sites/genetics
- Branchial Region/anatomy & histology
- Branchial Region/growth & development
- Branchial Region/metabolism
- Carrier Proteins/genetics
- Carrier Proteins/metabolism*
- Cell Line
- Chromatin/metabolism
- Gene Expression Regulation, Developmental
- Histone Acetyltransferases/genetics
- Histone Acetyltransferases/metabolism
- Histones/metabolism*
- Humans
- Immunoprecipitation
- In Situ Hybridization
- Mice
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism*
- Protein Binding
- Recombinant Proteins/metabolism
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 18469222 Full text @ Development
Citation
Laue, K., Daujat, S., Crump, J.G., Plaster, N., Roehl, H.H., Tübingen 2000 Screen Consortium, Kimmel, C.B., Schneider, R., and Hammerschmidt, M. (2008) The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity. Development (Cambridge, England). 135(11):1935-1946.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping