Sox2 cooperates with Chd7 to regulate genes that are mutated in human syndromes

作者：Engelen Erik; Akinci Umut; Bryne Jan Christian; Hou Jun; Gontan Cristina; Moen Maaike; Szumska Dorota; Kockx Christel; van IJcken Wilfred; Dekkers Dick H W; Demmers Jeroen; Rijkers Erik Jan; Bhattacharya Shoumo; Philipsen Sjaak; Pevny Larysa H; Grosveld Frank G; Rottier Robbert J; Lenhard Boris; Poot Raymond A^*

来源：Nature Genetics, 2011, 43(6): 607-U153.

DOI：10.1038/ng.825

The HMG-box transcription factor Sox2 plays a role throughout neurogenesis(1) and also acts at other stages of development(2), as illustrated by the multiple organs affected in the anophthalmia syndrome caused by SOX2 mutations(3-5). Here we combined proteomic and genomic approaches to characterize gene regulation by Sox2 in neural stem cells. Chd7, a chromatin remodeling ATPase associated with CHARGE syndrome(6,7), was identified as a Sox2 transcriptional cofactor. Sox2 and Chd7 physically interact, have overlapping genome-wide binding sites and regulate a set of common target genes including Jag1, Gli3 and Mycn, genes mutated in Alagille, Pallister-Hall and Feingold syndromes, which show malformations also associated with SOX2 anophthalmia syndrome or CHARGE syndrome(8-10). Regulation of disease-associated genes by a Sox2-Chd7 complex provides a plausible explanation for several malformations associated with SOX2 anophthalmia syndrome or CHARGE syndrome. Indeed, we found that Chd7-haploinsufficient embryos showed severely reduced expression of Jag1 in the developing inner ear.

• 出版日期2011-6