Promoter-specific targeting of human SWI-SNF complex by Epstein-Barr virus nuclear protein 2.
The multiprotein human SWI-SNF (hSWI-SNF) complex is a chromatin-remodeling machine that facilitates transcription by overcoming chromatin-mediated gene repression. We had previously shown that hSNF5/INI1, an intrinsic, consistent component of the hSWI/SNF complex, is associated with Epstein-Barr nuclear antigen 2 (EBNA2) and have proposed that EBNA2 directs this complex to key EBNA2-responsive viral and cellular genes. Using chromatin immunoprecipitation and quantitative PCR, we show that antibodies directed against components of the hSWI-SNF complex preferentially precipitate chromatin-associated DNA that contains a targeted EBNA2-responsive element in the context of both episomal and cellular chromatin. This enrichment does not occur in EBNA2-negative cells or when the EBNA2-responsive element is mutated. The stable association of the hSWI-SNF complex with the EBNA2-responsive promoter can also be disrupted by deletion of the TATA element, suggesting that EBNA2 in itself is insufficient to mediate stable targeting of the hSWI-SNF complex. These results demonstrate that recruitment of the hSWI-SNF complex to selected promoters can occur in vivo through its interaction with site-specific activator proteins and that stable targeting may require the presence of basal transcription factors.
Wu
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Division of Medical Oncology, Department of Medicine, Veterans Administration Puget Sound Health Care System, Seattle Division, Seattle, Washington 98108, USA.
Krumm
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Schubach
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D001483:Base Sequence; D002472:Cell Transformation, Viral; D002843:Chromatin / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
D002843:Chromatin; C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D009687:Nuclear Proteins; D014764:Viral Proteins