Transcriptional Regulation of the α-fetoprotein Gene by SWI/SNF Chromatin Remodeling Complex

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Abstract
α-Fetoprotein (AFP) is a fetal serum protein abundant in fetal liver whose expression is downregulated in adult liver. The promoter–proximal region of the AFP gene contains two binding sites for CCAAT/enhancer-binding protein α (C/EBPα), two for hepatocyte nuclear factor-1α (HNF-1α) and one for nuclear factor-1 (NF-1). Luciferase reporter assays showed that a combination of C/EBPα, HNF-1α, NF-1 and coactivator p300 gave the maximal activity but the BRG1 and BRM, ATPase subunit of the chromatin remodeling complex SWI/SNF, repressed the transactivation of the AFP gene by these transcription factors. Deletion analyses of C/EBPα binding sites suggested that C/EBPα recruited SWI/SNF complex and caused the repression. This repression may also play important roles in the downregulation of the AFP gene in adult hepatocytes.

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