A position-effect assay for boundaries of higher order chromosomal domains

Kellum, Rebecca; Schedl, Paul

doi:10.1016/0092-8674(91)90318-s

Cited by 602 publications

(419 citation statements)

References 30 publications

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“…It has been shown that they are associated with constitutive HS sites and establish higher-order domains of chromatin that affect the interaction between enhancers and promoters (9,20). For example, the "specialized chromatin structures" at the boundaries of the Drosophila hsp70 genes, which are associated with multiple DNase I HS sites, can insulate the white gene from both positive and negative chromosomal position effects and can insulate the hsp70 promoter from activation by enhancers (29,55). Specific peptides (BEAF-32A and BEAF-32B) are constitutively bound to these elements, and immunostaining localizes these factors to interband regions and puffs of polytene chromosomes, suggesting a role in the organization of chromosomal domains (25,60).…”

Section: Discussionmentioning

confidence: 99%

Parental Allele-Specific Chromatin Configuration in a Boundary–Imprinting-Control Element Upstream of the Mouse H19 Gene

Khosla

Aitchison

Gregory

et al. 1999

Molecular and Cellular Biology

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The mouse H19 gene is expressed from the maternal chromosome exclusively. A 2-kb region at 2 to 4 kb upstream of H19 is paternally methylated throughout development, and these sequences are necessary for the imprinted expression of both H19 and the 5 -neighboring Igf2 gene. In particular, on the maternal chromosome this element appears to insulate the Igf2 gene from enhancers located downstream of H19. We analyzed the chromatin organization of this element by assaying its sensitivity to nucleases in nuclei. Six DNase I hypersensitive sites (HS sites) were detected on the unmethylated maternal chromosome exclusively, the two most prominent of which mapped 2.25 and 2.75 kb 5 to the H19 transcription initiation site. Five of the maternal HS sites were present in expressing and nonexpressing tissues and in embryonic stem (ES) cells. They seem, therefore, to reflect the maternal origin of the chromosome rather than the expression of H19. A sixth maternal HS site, at 3.45 kb upstream of H19, was detected in ES cells only. The nucleosomal organization of this element was analyzed in tissues and ES cells by micrococcal nuclease digestion. Specifically on the maternal chromosome, an unusual and strong banding pattern was obtained, suggestive of a nonnucleosomal organization. From our studies, it appears that the unusual chromatin organization with the presence of HS sites (maternal chromosome) and DNA methylation (paternal chromosome) in this element are mutually exclusive and reflect alternate epigenetic states. In addition, our data suggest that nonhistone proteins are associated with the maternal chromosome and that these might be involved in its boundary function.

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Section: Discussionmentioning

confidence: 99%

Parental Allele-Specific Chromatin Configuration in a Boundary–Imprinting-Control Element Upstream of the Mouse H19 Gene

Khosla

Aitchison

Gregory

et al. 1999

Molecular and Cellular Biology

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“…Insulators act as dominant repressors that function over long distances to block interactions between cis-elements and inappropriate promoters [157]. For example, a 340 bp insulator DNA within the Drosophila gypsy retrotransposon disrupts gene activity by blocking the interactions of distal enhancers with target promoters [158].…”

Section: Insulatorsmentioning

confidence: 99%

“…Scs and scsh, which flank the Drosophila hsp70 locus, are perhaps the best characterized and most understood authentic insulators [157] and are mechanistically indistinguishable from the gypsy insulator [158]. It is believed that insulators might block distal enhancers via DNA bending, mimicking the structural changes mediated by TFIID binding to the promoter [159,160].…”

Section: Insulatorsmentioning

confidence: 99%

Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes

Ogbourne

Antalis

1998

Biochemical Journal

222

171

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Mechanisms controlling transcription and its regulation are fundamental to our understanding of molecular biology and, ultimately, cellular biology. Our knowledge of transcription initiation and integral factors such as RNA polymerase is considerable, and more recently our understanding of the involvement of enhancers and complexes such as holoenzyme and mediator has increased dramatically. However, an understanding of transcriptional repression is also essential for a complete understanding of promoter structure and the regulation of gene expression. Transcriptional repression in eukaryotes is achieved through ‘silencers ’, of which there are two types, namely ‘silencer elements ’ and ‘negative regulatory elements ’ (NREs). Silencer elements are classical, position-independent elements that direct an active repression mechanism, and NREs are position-dependent elements that direct a passive repression mechanism. In addition, ‘repressors ’ are DNA-binding trasncription factors that interact directly with silencers. A review of the recent literature reveals that it is the silencer itself and its context within a given promoter, rather than the interacting repressor, that determines the mechanism of repression. Silencers form an intrinsic part of many eukaryotic promoters and, consequently, knowledge of their interactive role with enchancers and other transcriptional elements is essential for our understanding of gene regulation in eukaryotes.

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“…Well-known examples of protective insulators include the cHS4 element from the chick b-globin locus [11][12][13] , the scs and scs¢ sequences from the Drosophila HSP70 locus 14 and the su(Hw) binding element from the gypsy retrovirus 15 . However, although insulators can decrease variability in some contexts, it remains unclear whether they permit optimal transgene regulation and high levels of expression 12,14,16,17 . Moreover, insulators do not seem to have robust activity at all loci, thereby limiting their utility 12,15 .…”

mentioning

confidence: 99%

Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes

et al. 2008

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A position-effect assay for boundaries of higher order chromosomal domains

Cited by 602 publications

References 30 publications

Parental Allele-Specific Chromatin Configuration in a Boundary–Imprinting-Control Element Upstream of the Mouse H19 Gene

Parental Allele-Specific Chromatin Configuration in a Boundary–Imprinting-Control Element Upstream of the Mouse H19 Gene

Transcriptional control and the role of silencers in transcriptional regulation in eukaryotes

Exploiting position effects and the gypsy retrovirus insulator to engineer precisely expressed transgenes

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