title: Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control.
abstract: Understanding how transcriptional enhancers control over 20,000 protein-coding genes to maintain cell-type-specific gene expression programs in all human cells is a fundamental challenge in regulatory biology. Recent studies suggest that gene regulatory elements and their target genes generally occur within insulated neighborhoods, which are chromosomal loop structures formed by the interaction of two DNA sites bound by the CTCF protein and occupied by the cohesin complex. Here, we review evidence that insulated neighborhoods provide for specific enhancer-gene interactions, are essential for both normal gene activation and repression, form a chromosome scaffold that is largely preserved throughout development, and are perturbed by genetic and epigenetic factors in disease. Insulated neighborhoods are a powerful paradigm for gene control that provides new insights into development and disease.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: hnisz@wi.mit.edu.
authors.forename: Denes
authors.initials: D
authors.lastname: Hnisz
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Electronic address: dsday@wi.mit.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Day
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: young@wi.mit.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002875:Chromosomes / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D038101:Insulator Elements; D008322:Mammals / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D012097:Repressor Proteins