spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 29 August 2007
doi: 10.1242/dev.004481

Development 134, 3507-3515 (2007)
Published by The Company of Biologists 2007
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.004481v1
134/19/3507    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in Development
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shang, E.
Right arrow Articles by Wolgemuth, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shang, E.
Right arrow Articles by Wolgemuth, D. J.

The first bromodomain of Brdt, a testis-specific member of the BET sub-family of double-bromodomain-containing proteins, is essential for male germ cell differentiation

Enyuan Shang1, Helen D. Nickerson2, Duancheng Wen3, Xiangyuan Wang4 and Debra J. Wolgemuth1,2,4,5,6,*

1 The Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032, USA.
2 Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
3 The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
4 Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY 10032, USA.
5 The Center for Reproductive Sciences, Columbia University Medical Center, New York, NY 10032, USA.
6 The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.

* Author for correspondence (e-mail: djw3{at}columbia.edu)

Accepted 22 July 2007

Brdt is a testis-specific member of the distinctive BET sub-family of bromodomain motif-containing proteins, a motif that binds acetylated lysines and is implicated in chromatin remodeling. Its expression is restricted to the germ line, specifically to pachytene and diplotene spermatocytes and early spermatids. Targeted mutagenesis was used to generate mice carrying a mutant allele of Brdt, Brdt{Delta}BD1, which lacks only the first of the two bromodomains that uniquely characterize BET proteins. Homozygous Brdt{Delta}BD1/{Delta}BD1 mice were viable but males were sterile, producing fewer and morphologically abnormal sperm. Aberrant morphogenesis was first detected in step 9 elongating spermatids, and those elongated spermatids that were formed lacked the distinctive foci of heterochromatin at the peri-nuclear envelope. Quantitative reverse transcription (RT)-PCR showed threefold increased levels of histone H1t (Hist1h1t) in Brdt{Delta}BD1/{Delta}BD1 testes and chromatin immunoprecipitation revealed that Brdt protein, but not Brdt{Delta}BD1 protein, was associated with the promoter of H1t. Intracytoplasmic sperm injection suggested that the DNA in the Brdt{Delta}BD1 mutant sperm could support early embryonic development and yield functional embryonic stem cells. This is the first demonstration that deletion of just one of the two bromodomains in members of the BET sub-family of bromodomain-containing proteins has profound effects on in vivo differentiation.

Key words: Brdt, Bromodomain, Spermatogenesis, Mouse


Related articles in Development:

BETs on for spermatogenesis

Development 2007 134: e1902. [Full Text]  





© The Company of Biologists Ltd 2007