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  • Title: RFXB and its splice variant RFXBSV mediate the antagonism between IFNgamma and TGFbeta on COL1A2 transcription in vascular smooth muscle cells.
    Author: Fang M, Kong X, Li P, Fang F, Wu X, Bai H, Qi X, Chen Q, Xu Y.
    Journal: Nucleic Acids Res; 2009 Jul; 37(13):4393-406. PubMed ID: 19465385.
    Abstract:
    Cytokines secreted by infiltrating immune cells during atherogenesis modulate vascular remodeling. One exemplary event is the antagonism between transformed growth factor (TGF-beta) and interferon gamma (IFN-gamma) on the transcriptional control of type I collagen gene (COL1A2). Previously we have reported that IFN-gamma up-regulates regulatory factor for X-box B (RFXB) to repress collagen transcription while down-regulates the expression of RFXBSV, a splice variant of RFXB that blocks collagen repression in fibroblasts. Here we demonstrate that TGF-beta abrogated COL1A2 repression by IFN-gamma through altering the relative expression of RFXB and RFXBSV. Unlike RFXB, RFXBSV did not bind to the collagen promoter and competed with RFXB for the co-repressor histone deacetylase 2 (HDAC2), limiting HDAC2 recruitment to the collagen transcription start site as evidenced by chromatin immunoprecipitation assays. Over-expression of RFXB by lentiviral infection in HASMCs enhanced HDAC2 enlistment, promoted histone deacetylation surrounding the collagen site by IFN-gamma, and blocked the TGF-beta antagonism, a pattern reversed by RFXBSV infection. On the contrary, silencing of RFXB, but not both RFXB and RFXBSV, expression promoted the TGF-beta antagonism. Thus, we have identified a novel mechanism whereby TGF-beta antagonizes the IFN-gamma repression of collagen transcription in HASMCs and as such provided new insights into antiatherogenic strategies.
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