Identification of unique, differentiation stage-specific patterns of expression of the bromodomain-containing genes Brd2, Brd3, Brd4, and Brdt in the mouse testis.
The bromodomain, an evolutionarily conserved motif that binds acetyl-lysine on histones, is found in many chromatin-associated proteins, transcription factors, and in nearly all known histone acetyltransferases. The BET subclass of bromodomain-containing proteins contains two bromodomains and one ET domain and consists of at least four members in mouse and human, Brd2, Brd3, Brd4, and Brdt. We isolated mouse cDNAs for these genes and studied their expression patterns with particular focus on the testis. Northern hybridization revealed that Brd3 is most abundant in testis, ovary, placenta, uterus, and brain; that Brd4 is rather ubiquitously expressed but is most abundant in mid-gestation embryo, testis, ovary, and brain; and that Brdt is specifically expressed in testis. In situ hybridization and immunostaining on histological sections of mouse testes revealed a strikingly specific and dynamic change of cellular specificity in the germ line during the progression of spermatogenesis. Brd4 is expressed in spermatogonia, Brdt is only expressed in mid- to late-spermatocytes, Brd2 is expressed in diplotene spermatocytes and round spermatids and at low levels in spermatogonia, and Brd3 is expressed in round spermatids. This unique expression pattern suggests that genes in this subclass are not simply redundant. Rather, their expression is tightly regulated in the male germ cell lineage, suggesting that they likely have specific roles in different developmental stages and/or cell types.
Shang
Enyuan
E
The Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032, USA.
Salazar
Glicella
G
Crowley
Thomas E
TE
Wang
Xiang
X
Lopez
Rocio A
RA
Wang
Xiangyuan
X
Wolgemuth
Debra J
DJ
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002868:Chromosomal Proteins, Non-Histone; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008297:Male; D051379:Mice / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D018076:DNA, Complementary; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; C490844:Brd2 protein, mouse; D000092468:Bromodomain Containing Proteins; C518476:Brd3 protein, mouse; C486694:Brd4 protein, mouse