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Transforming growth factor-beta (TGFbeta) signaling is important in fibrotic disorders. It promotes protein expression of the receptor TGFbeta receptor type II (TbetaRII), which regulates the expression of specific genes. We recently identified the HMG box transcription factor Sip1 as an intracellular partner of TbetaRII. Sip1 recognizes a cis-acting element in the TbetaRIIs promoter. In this study, we present that transcription factor MEF2C and its cofactor MRTF-A and -C interact with Sip1 and regulate its recruitment to the TbetaRIIs promoter. We identified the transcription factor MEF2C as a new binding partner of the cofactor MRTF-A and -C. We show that Sip1, as well as the actin related proteins MRTF-A and -C, as well as MEF2C localize to the nucleus. Furthermore, the MRTFs are involved in the recruitment of Sip1 to the TbetaRIIs promoter. This recruitment is mimicked by depleting endogenous MRTF-A and -C, but not by depletion of endogenous MEF2C. In contrast, depletion of MRTF-A and -C increases the recruitment of Sip1 to the TbetaRIIs promoter. MRTF-dependent recruitment of Sip1 to the TbetaRIIs promoter correlates with a reduced activity of this promoter. We also show that ectopic expression of MEF2
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