| First Author | Chandler RL | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 2 | Pages | 265-80 |
| PubMed ID | 23129809 | Mgi Jnum | J:192829 |
| Mgi Id | MGI:5466629 | Doi | 10.1128/MCB.01008-12 |
| Citation | Chandler RL, et al. (2013) ARID1a-DNA interactions are required for promoter occupancy by SWI/SNF. Mol Cell Biol 33(2):265-80 |
| abstractText | Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of the complex, physiological roles for this domain remain undefined. Here, we show that disruption of ARID1a-DNA binding in mice results in embryonic lethality, with mutant embryos manifesting prominent defects in the heart and extraembryonic vasculature. The DNA binding-defective mutant ARID1a subunit is stably expressed and capable of assembling into a SWI/SNF complex with core catalytic properties, but nucleosome substrate binding and promoter occupancy by ARID1a-containing SWI/SNF complexes (BAF-A) are impaired. Depletion of ARID domain-dependent, BAF-A associations at THROMBOSPONDIN 1 (THBS1) led to the concomitant upregulation of this SWI/SNF target gene. Using a THBS1 promoter-reporter gene, we further show that BAF-A directly regulates THBS1 promoter activity in an ARID domain-dependent manner. Our data not only demonstrate that ARID1a-DNA interactions are physiologically relevant in higher eukaryotes but also indicate that these interactions facilitate SWI/SNF binding to target sites in vivo. These findings support the model wherein cooperative interactions among intrinsic subunit-chromatin interaction domains and sequence-specific transcription factors drive SWI/SNF recruitment. |
