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Biochim Biophys Acta. 2012 Jul;1819(7):644-51. doi: 10.1016/j.bbagrm.2012.01.016. Epub 2012 Feb 2.

Chromatin domains, insulators, and the regulation of gene expression.

Author information

1
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Key Diseases, National Insitute of Health, 9000 Rockville Pike, Bethesda, MD 20892-0540, USA.

Abstract

The DNA sequence elements called insulators have two basic kinds of properties. Barrier elements block the propagation of heterochromatic structures into adjacent euchromatin. Enhancer blocking elements interfere with interaction between an enhancer and promoter when placed between them. We have dissected a compound insulator element found at the 5' end of the chicken β-globin locus, which possesses both activities. Barrier insulation is mediated by two kinds of DNA binding proteins: USF1/USF2, a heterodimer which recruits multiple enzyme complexes capable of marking histone on adjacent nucleosomes with 'activating' marks, and Vezf1, which protects against DNA methylation. We have found that the heterochromatic region upstream of the insulator element is maintained in its silent state by a dicer-dependent mechanism, suggesting a mechanism for Vezf1 function in the insulator. Enhancer blocking function in the β-globin insulator element is conferred by a binding site for CTCF. Consistent with this property, CTCF binding was found some years ago to be essential for imprinted expression at the Igf2/H19 locus. Work in many laboratories has since demonstrated that CTCF helps stabilize long-range interactions in the nucleus. We have recently shown that in the case of the human insulin locus such an interaction, over a distance of ~300kb, can result in stimulation of a target gene which itself is important for insulin secretion. This article is part of a Special Issue entitled: Chromatin in time and space.

PMID:
22326678
PMCID:
PMC3484685
DOI:
10.1016/j.bbagrm.2012.01.016
[Indexed for MEDLINE]
Free PMC Article

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