Epstein-Barr virus nuclear antigen 3C recruits histone deacetylase activity and associates with the corepressors mSin3A and NCoR in human B-cell lines.
Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is a known regulatory transcription factor that has been shown to interact with histone deacetylase 1 (HDAC1) when cotransfected in human cell lines and by in vitro binding experiments. Previous studies have shown that EBNA3C interacts with p300 and prothymosin alpha (ProTalpha) in EBV-infected cells and may be involved in recruiting acetyltransferases to the chromatin for acetylation of histones and transcriptional activation. EBNA3C has also been shown to function as a repressor of transcription when directed to promoters. In this report, we show that EBNA3C complexed with ProTalpha can also recruit deacetylase activity and associates in a complex that includes HDAC1 and HDAC2 in human B cells. A complex of EBNA3C and ProTalpha coimmunoprecipitated with HDAC1 and HDAC2 in cell lines stably expressing EBNA3C. Additionally, this complex associated with the mSin3A and NCoR corepressors in EBNA3C-expressing cell lines and may function in a complex with additional transcription factors known to be repressors of transcription. EBNA3C in complex with ProTalpha recruited deacetylase activity in cell lines stably expressing EBNA3C, and this activity was shown to be partially sensitive to trichostatin A (TSA). This suggests an association with other deacetylases that are insensitive to the general inhibitory effects of TSA, as the entire activity was not abolished in multiple assays. The association between EBNA3C and the corepressors as well as HDACs is likely to depend on the presence of ProTalpha in the complex. Immunoprecipitation with anti-ProTalpha antibody immunoprecipitated EBNA3C and the other repressors, whereas immunoprecipitation with anti-EBNA3C antibody resulted in little or no association with these molecules associated with transcription repression. Clearly, EBNA3C functions as a component of a number of dynamic complexes which function in repression and activation of transcription.
Knight
Jason S
JS
Department of Microbiology and Abramson Comprehensive Cancer Center, University of Pennsylvania Medical School, Philadelphia 19104, USA.
Lan
Ke
K
Subramanian
Chitra
C
Robertson
Erle S
ES
D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002472:Cell Transformation, Viral; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D011233:Precipitin Tests; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C539127:NCOR1 protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011498:Protein Precursors; D011994:Recombinant Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C040782:prothymosin alpha; D013947:Thymosin; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex