All-Trans Retinoic Acid Induces Chromatin Remodeling at the Promoter of the Mouse Liver, Bone, and Kidney Alkaline Phosphatase Gene in C3H10T 1/2 Cells

作者：Wan, Yang; Yang, Songhai; Sun, Fenyong; Wang, Jiayi; Chen, Qiongyu; Hong, An^*

来源：Biochemical Genetics, 2012, 50(7-8): 495-507.

DOI：10.1007/s10528-011-9494-9

• Osteoblast differentiation
• Bone formation
• Gene regulation
• Histone modifications
• MAPK pathway

The alkaline phosphatase (ALP) gene is an important marker of osteoblast differentiation and bone formation. Although the molecular mechanisms of increased ALP expression in response to all-trans retinoic acid (ATRA) have been reported, the role of ATRA in chromatin structure changes remains unknown. Our results show that the expression of mouse liver, bone, and kidney ALP (mL/B/K-ALP) induced by ATRA in C3H10T 1/2 cells was related to the retinoic acid nuclear receptors, RAR alpha and RAR beta, which are not involved in the MAPK pathway. DNase I hypersensitivity analysis revealed an inducible hypersensitive site in the mL/B/K-ALP promoter at similar to 520 bp upstream of the transcription start site. Chromatin immunoprecipitation experiments showed a cascade of transcription cofactor recruitment events during ATRA-induced upregulation of mL/B/K-ALP. Together, our results provide a link between ATRA-induced mL/B/K-ALP gene transcription and chromatin remodeling.

• 出版日期2012-8
• 单位上海交通大学; 上海市闵行区中心医院; 暨南大学