Insulators are fundamental components of the eukaryotic genomes

Abstract

The properties of cis-regulatory elements able to influence gene transcription over large distances have led to the hypothesis that elements called insulators should exist to limit the action of enhancers and silencers. During the last decades, insulators have been identified in many eukaryotes from yeast to human. Insulators possess two main properties: (i) they can block enhancer-promoter communication ('enhancer blocker activity'), and (ii) they can prevent the spread of repressive chromatin ('barrier activity'). This review focuses on recent studies designed to elucidate the molecular mechanisms of the insulator function, and gives an overview of the critical role of insulators in nuclear organization and functional identity of chromatin. Heredity (2005) 94, 571-576.

Disruption of Topoisomerase II Perturbs Pairing in Drosophila Cell Culture

“…Indeed, interactions between nonhomologous chromosomal regions may be as potent as those between homologous regions and, as may be the case with homologous pairing, have the capacity to persist through and be regulated by mitosis. Such nonhomologous interactions range from those ensuing from the clustering of PREs (Grimaud et al 2006) and insulators scattered throughout the genome (reviewed by Kuhn and Geyer 2003;Capelson and Corces 2004;Brasset and Vaury 2005;Gaszner and Felsenfeld 2006;Valenzuela and Kamakaka 2006) to those occurring in transcription factories (reviewed by Dillon 2006;Faro-Trindade and Cook 2006;Fraser 2006). Excitingly, they also include gene-specific interactions, such as those that occur in mammals between enhancers and distant promoters during olfactory receptor choice (Lomvardas et al 2006), between the interferon-g and T H 2 cytokine loci during T-cell development (Spilianakis et al 2005), and between the insulin-like growth factor 2/ H19 imprinting control region and the chromosomal segment containing the Wsb1 and Nf1 loci in a manner that appears to require the CCCTC binding factor CTCF (Ling et al 2006).…”

“…Of note, two factors that work in conjunction with the gypsy insulator, Suppressor of Hairy Wing ½Su(Hw) and Modifier of mdg4 ½Mod(mdg4) (Kravchenko et al 2005), colocalize at hundreds of chromosomal sites that do not correspond to gypsy elements and, along with another protein, Centrosomal Protein 190 (CP190), mediate the clustering of these sites into ''insulator bodies'' (reviewed by Kuhn and Geyer 2003;Capelson and Corces 2004;Brasset and Vaury 2005;Gaszner and Felsenfeld 2006;Valenzuela and Kamakaka 2006). Consistent with this finding, loss of Su(Hw) function has been observed to compromise homolog pairing (Fritsch et al 2006).…”

“…Another genetic element implicated in long-range interactions between homologous chromosomal regions is an insulator carried by the gypsy retrotransposon (reviewed by Kuhn and Geyer 2003;Capelson and Corces 2004;Brasset and Vaury 2005;Gaszner and Felsenfeld 2006;Valenzuela and Kamakaka 2006; also see Kravchenko et al 2005). Of note, two factors that work in conjunction with the gypsy insulator, Suppressor of Hairy Wing ½Su(Hw) and Modifier of mdg4 ½Mod(mdg4) (Kravchenko et al 2005), colocalize at hundreds of chromosomal sites that do not correspond to gypsy elements and, along with another protein, Centrosomal Protein 190 (CP190), mediate the clustering of these sites into ''insulator bodies'' (reviewed by Kuhn and Geyer 2003;Capelson and Corces 2004;Brasset and Vaury 2005;Gaszner and Felsenfeld 2006;Valenzuela and Kamakaka 2006).…”

New Properties of Drosophila Fab-7 Insulator

“…In this relation, of interest is the class of DNA sequence elements, named insulators, that contribute to the organization of independent gene function domains by restricting the functions of enhancers and silencers (Sun and Elgin 1999;Capelson and Corces 2004;Brasset and Vaury 2005;West and Fraser 2005;Gaszner and Felsenfeld 2006;Valenzuela and Kamakaka 2006). Insulators are characterized by two properties.…”

Maps of cis-Regulatory Nodes in Megabase Long Genome Segments are an Inevitable Intermediate Step Toward Whole Genome Functional Mapping

“…Two classes of sequences were supposed to be border elements that form and support the loop domain structure -insulators (reviewed in [28][29][30]) and scaffold/matrix attachment regions (S/MARs), defined as sequences capable of specific binding to nuclear matrix in vitro (reviewed in [31]). …”