Chromatin boundaries, insulators, and long-range interactions in the nucleus.
Within the genome, expressed genes marked by "open" chromatin are often adjacent to silent, heterochromatic regions. There are also regions containing neighboring active genes with different programs of expression. In both cases, DNA sequence elements may function as insulators, either providing barriers that prevent the incursion of heterochromatic signals into open domains or acting to block inappropriate contact between the enhancer of one gene and the promoter of another. The mechanisms associated with insulation are diverse: Enhancer-blocking insulation is largely associated with the ability to stabilize the formation of loop domains within the nucleus. Barrier insulation is often associated with the ability to block propagation of silencing histone modifications. Here, we provide examples of both kinds of insulator action, derived initially from studies of the compound insulator element at the 5' end of the chicken β-globin locus. Such elements appear to have more general regulatory roles in the genome that have been exploited to provide insulator function where necessary to demarcate separate domains within the nucleus.
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0540, USA.
K E
KE
Giles
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H
Gowher
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R
Ghirlando
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C
Jin
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G
Felsenfeld
D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000076246:CCCTC-Binding Factor; D002645:Chickens; D002843:Chromatin / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006570:Heterochromatin / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D038101:Insulator Elements / Q000235:genetics*; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D055544:beta-Globins / Q000235:genetics; D000097584:DNA Methyltransferase 3B
D000076246:CCCTC-Binding Factor; D002843:Chromatin; D004248:DNA (Cytosine-5-)-Methyltransferases; D006570:Heterochromatin; D006877:Hydroxamic Acids; D012097:Repressor Proteins; D043244:Ribonuclease III; D055544:beta-Globins; D000097584:DNA Methyltransferase 3B; C012589:trichostatin A