Mutations in the fibrillin-1 gene (FBN1) cause Marfan Syndrome (MFS), a hereditary disorder of connective tissue. The transcription of FBN1 has been reported to be driven by a short ultraconserved region (SUPR) in the 5' untranslated exon A of FBN1, but the nature of other factors involved in FBN1 gene regulation has not been clarified. In this study, we characterized the transcription factors involved in FBN1 gene regulation. The results show that Sp1 protein binds to two putative binding sites in the promoter of FBN1. Overexpression of Sp1 resulted in a significant increase in both promoter activity and FBN1 mRNA level in HEK 293 cells, whereas inhibition or knockdown of Sp1 decreased FBN1 gene expression. In addition, we found that Poly [ADP-ribose] polymerase 1 (PARP1) binds to the palindromic sequence TCTCGCGAGA in the ultraconserved region of the FBN1 promoter and that the regulation of FBN1 expression by PARP1 is dependent on Sp1. These results indicate that both Sp1 and PARP1 contribute to FBN1 gene expression. These observations add to our understanding of the transcriptional regulation of FBN1 gene expression.
Keywords: DPE; FBN1; Initiator; Inr; MFS; Marfan syndrome; PARP1; Poly [ADP-ribose] polymerase 1; SUPR; Sp1; downstream promoter element; fibrillin-1; short ultraconserved promoter region; specificity protein 1.