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

Full 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.

Author information

Author/s: Mutskov, Vesco (V); Felsenfeld, Gary (G);

Affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Intramural

Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A), published in United States. (Language: eng)

Reference: 2009-Oct; vol 106 (issue 41) : pp 17419-24

Dates: Created 2009/10/15; Completed 2009/11/03; Revised 2009/11/06;

PMID: 19805079, status: MEDLINE (last retrieval date: 11/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Chromatin - genetics
Diabetes Mellitus, Type 1 - genetics
Female
Gene Expression Regulation
Humans
Insulin - genetics
Insulin-Like Growth Factor II - genetics

Associated Chemicals: Chromatin (0) ; IGF2AS protein, human (0) ; Proteins (0) ; Insulin (11061-68-0) ; Insulin-Like Growth Factor II (67763-97-7) ; Tyrosine 3-Monooxygenase (EC 1.14.16.2)

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