Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis.
Many transcription factors regulate specific temporal-spatial events during cardiac differentiation; however, the mechanisms that regulate such events are largely unknown. Using a modified subtractive hybridization method to identify specific genes that influence early cardiac development, we found that Bop is expressed specifically in cardiac and skeletal muscle precursors before differentiation of these lineages. Bop encodes a protein containing MYND and SET domains, which have been shown to regulate transcription by mediating distinct chromatin modifications. We show that m-Bop is a histone deacetylase-dependent transcriptional repressor. Targeted deletion of Bop in mice disrupted maturation of ventricular cardiomyocytes and interfered with formation of the right ventricle. Normal expression of Hand2, a transcription factor essential for right ventricular development, in cardiomyocyte precursors is dependent upon m-Bop. These results indicate that m-Bop is essential for cardiomyocyte differentiation and cardiac morphogenesis.
Gottlieb
Paul D
PD
Section of Molecular Genetics and Microbiology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA. gottlieb@uts.cc.utexas.edu
Pierce
Stephanie A
SA
Sims
Robert J
RJ
Yamagishi
Hiroyuki
H
Weihe
Elizabeth K
EK
Harriss
June V
JV
Maika
Shanna D
SD
Kuziel
William A
WA
King
Heather L
HL
Olson
Eric N
EN
Nakagawa
Osamu
O
Srivastava
Deepak
D
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002642:Chick Embryo; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D006321:Heart / Q000196:embryology / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics; D006655:Histone Deacetylases / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D012097:Repressor Proteins; C096485:Smyd1 protein, mouse; D014157:Transcription Factors; D006655:Histone Deacetylases