XPD mutations in trichothiodystrophy hamper collagen VI expression and reveal a role of TFIIH in transcription derepression

• DOI: 10.1093/hmg/dds508
• Publication Date: 2012-12-08T07:43:31Z
• Authors: D. Orioli; E. Compe; T. Nardo; M. Mura; C. Giraudon; E. Botta; L. Arrigoni; F. A. Peverali; J. M. Egly; M. Stefanini
• Keywords: Derepression; Transcription

Mutations in the XPD subunit of transcription/DNA repair factor (TFIIH) give rise to trichothiodystrophy (TTD), a rare hereditary multisystem disorder with skin abnormalities. Here, we show that TTD primary dermal fibroblasts contain low amounts collagen type VI alpha1 (COL6A1), fundamental component soft connective tissues. We demonstrate COL6A1 expression is downregulated by sterol regulatory element-binding protein-1 (SREBP-1) whose removal from promoter key step transcription upregulation response cell confluence. provide evidence for TFIIH being involved derepression, thus highlighting new function gene regulation. The lack caused inability mutated complexes remove SREBP-1 and sustain subsequent high rate transcription. This defect might account pathologic features shares disorders because mutations COL6A genes.