Polybromo protein BAF180 functions in mammalian cardiac chamber maturation.
BAF and PBAF are two related mammalian chromatin remodeling complexes essential for gene expression and development. PBAF, but not BAF, is able to potentiate transcriptional activation in vitro mediated by nuclear receptors, such as RXRalpha, VDR, and PPARgamma. Here we show that the ablation of PBAF-specific subunit BAF180 in mouse embryos results in severe hypoplastic ventricle development and trophoblast placental defects, similar to those found in mice lacking RXRalpha and PPARgamma. Embryonic aggregation analyses reveal that in contrast to PPARgamma-deficient mice, the heart defects are likely a direct result of BAF180 ablation, rather than an indirect consequence of trophoblast placental defects. We identified potential target genes for BAF180 in heart development, such as S100A13 as well as retinoic acid (RA)-induced targets RARbeta2 and CRABPII. Importantly, BAF180 is recruited to the promoter of these target genes and BAF180 deficiency affects the RA response for CRABPII and RARbeta2. These studies reveal unique functions of PBAF in cardiac chamber maturation.
Wang
Zhong
Z
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3204, USA.
Zhai
Weiguo
W
Richardson
James A
JA
Olson
Eric N
EN
Meneses
Juanito J
JJ
Firpo
Meri T
MT
Kang
Chulho
C
Skarnes
William C
WC
Tjian
Robert
R
D000818:Animals; D002449:Cell Aggregation / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D024002:HMGB Proteins; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000002:abnormalities; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D009687:Nuclear Proteins; C496872:Pbrm1 protein, mouse; D018168:Receptors, Retinoic Acid; D009418:S100 Proteins; C511524:S100a13 protein, mouse; D014157:Transcription Factors; C082928:retinoic acid binding protein II, cellular; C082925:retinoic acid receptor beta