The human insulin gene is part of a large open chromatin domain specific for human islets

Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17419-24. doi: 10.1073/pnas.0909288106. Epub 2009 Sep 28.

Abstract

Knowledge of how insulin (INS) gene expression is regulated will lead to better understanding of normal and abnormal pancreatic beta 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 approximately 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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Chromatin / genetics*
  • Diabetes Mellitus, Type 1 / genetics
  • Female
  • Gene Expression Regulation
  • Humans
  • Insulin / genetics*
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Secreting Cells / physiology
  • Islets of Langerhans / physiology*
  • Multigene Family / genetics
  • Oligonucleotide Array Sequence Analysis
  • Polycystic Ovary Syndrome / genetics
  • Proteins / genetics
  • Tyrosine 3-Monooxygenase / genetics

Substances

  • Chromatin
  • IGF2-AS protein, human
  • Insulin
  • Proteins
  • Insulin-Like Growth Factor II
  • Tyrosine 3-Monooxygenase