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RESEARCH PAPER

Polybromo protein BAF180 functions in mammalian cardiac chamber maturation

¹ Department of Molecular and Cell Biology, ² Howard Hughes Medical Institute, University of California, Berkeley, California 94720-3204, USA; Departments of ³ Pathology and ⁴ Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA; ⁵ Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California 94143-0546, USA

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 RXR, VDR, and PPAR. 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 RXR and PPAR. Embryonic aggregation analyses reveal that in contrast to PPAR-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 RAR2 and CRABPII. Importantly, BAF180 is recruited to the promoter of these target genes and BAF180 deficiency affects the RA response for CRABPII and RAR2. These studies reveal unique functions of PBAF in cardiac chamber maturation.

[Keywords: Polybromo protein BAF180; PBAF (SWI/SNF6b); retinoic acid (RA) signaling; chromatin remodeling; heart; placenta]

Received July 8, 2004; revised version accepted October 12, 2004.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1238104.

⁶ Present address: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.

⁷ Corresponding author.
E-MAIL jmlim{at}uclink4.berkeley.edu; FAX (510) 643-9547.

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