Open AccessThe human insulin gene is part of a large open chromatin domain specific for human islets
Author(s) -
Vesco Mutskov,
Gary Felsenfeld
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0909288106
Subject(s) - biology , chromatin , gene expression , histone , gene , gene cluster , regulation of gene expression , islet , genetics , microbiology and biotechnology , insulin , endocrinology
Knowledge of how insulin (INS) gene expression is regulated will lead to better understanding of normal and abnormal pancreatic β cell function. We have mapped histone modifications over the INS region, coupled with an expression profile, in freshly isolated islets from multiple human donors. Unlike many other human genes, in which active modifications tend to be concentrated within 1 kb around the transcription start site, these marks are distributed over the entire coding region of INS as well. Moreover, a region of ≈80 kb around the INS gene, which contains the {tyrosine hydroxylase (TH)–(INS)–insulin-like growth factor 2 antisense (IGF2AS)–insulin-like growth factor 2 (IGF2)} gene cluster, unusually is marked by almost uniformly elevated levels of histone acetylation and H3K4 dimethylation, extending both downstream into IGF2 and upstream beyond the TH gene. This is accompanied by islet specific coordinate expression with INS of the neighboring TH and IGF2 genes. The presence of islet specific intergenic transcripts suggests their possible function in the maintenance of this unusual large open chromatin domain.