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. Author manuscript; available in PMC: 2014 Feb 15.
Published in final edited form as: Oncogene. 2012 Sep 10;32(33):3877–3885. doi: 10.1038/onc.2012.392

Figure 8.

Figure 8

Model of BR-Smad repression of PDGFA promoter activity. Earlier studies demonstrated that Sp1 mediates the basal transcription of the PDGFA gene through binding to four consensus binding sites in the proximal promoter region (denoted sites “A–D”). Based on ChIP data, we suggest that SMAD1 and SMAD5 bind to the proximal promoter region of PDGFA and block the “A” site for the Sp1 binding, thereby inhibiting gene expression. Loss of the BR-SMADs (SMAD1 and SMAD5) in ovarian granulosa cells thus allows Sp1 to bind to the “A” site and leads to increased PDGFA activation, possibly initiated cell proliferation and contributing to disease onset.