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Article: A dominant chromatin-opening activity in 5 hypersensitive site 3 of the human β-globin locus control region

TitleA dominant chromatin-opening activity in 5 hypersensitive site 3 of the human β-globin locus control region
Authors
Keywordsβ-globin
Chromatin
Locus control region
Issue Date1996
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emboj/index.html
Citation
Embo Journal, 1996, v. 15 n. 3, p. 562-568 How to Cite?
AbstractSingle-copy human β-globin transgenes are very susceptible to suppression by position effects of surrounding closed chromatin. However, these position effects are overcome by a 20 kbp DNA fragment containing the locus control region (LCR). Here we show that the 6.5 kbp microlocus LCR cassette reproducibly directs full expression from independent single-copy β-globin transgenes. By testing individual DNase I-hypersensitive sites (HS) present in the microlocus cassette, we demonstrate that the 1.5 kbp 5′HS2 enhancer fragment does not direct β-globin expression from single-copy transgenes. In contrast, the 1.9 kbp 5′HS3 fragment directs β-globin expression in five independent single-copy transgenic mouse lines. Moreover, the 5′HS3 core element and β-globin proximal promoter sequences are DNase I hypersensitive in fetal liver nuclei of these expressing transgenic lines. Taken together, these results demonstrate that LCR activity is the culmination of at least two separable functions including: (i) a novel activity located in 5′HS3 that dominantly opens and remodels chromatin structure; and (ii) a recessive enhancer activity residing in 5′HS2. We postulate that the different elements of the LCR form a 'holocomplex' that interacts with the individual globin genes.
Persistent Identifierhttp://hdl.handle.net/10722/49427
ISSN
2015 Impact Factor: 9.643
2015 SCImago Journal Rankings: 7.450
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorEllis, Jen_HK
dc.contributor.authorTanUn, KCen_HK
dc.contributor.authorHarper, Aen_HK
dc.contributor.authorMichalovich, Den_HK
dc.contributor.authorYannoutsos, Nen_HK
dc.contributor.authorPhilipsen, Sen_HK
dc.contributor.authorGrosveld, Fen_HK
dc.date.accessioned2008-06-12T06:42:24Z-
dc.date.available2008-06-12T06:42:24Z-
dc.date.issued1996en_HK
dc.identifier.citationEmbo Journal, 1996, v. 15 n. 3, p. 562-568en_HK
dc.identifier.issn0261-4189en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49427-
dc.description.abstractSingle-copy human β-globin transgenes are very susceptible to suppression by position effects of surrounding closed chromatin. However, these position effects are overcome by a 20 kbp DNA fragment containing the locus control region (LCR). Here we show that the 6.5 kbp microlocus LCR cassette reproducibly directs full expression from independent single-copy β-globin transgenes. By testing individual DNase I-hypersensitive sites (HS) present in the microlocus cassette, we demonstrate that the 1.5 kbp 5′HS2 enhancer fragment does not direct β-globin expression from single-copy transgenes. In contrast, the 1.9 kbp 5′HS3 fragment directs β-globin expression in five independent single-copy transgenic mouse lines. Moreover, the 5′HS3 core element and β-globin proximal promoter sequences are DNase I hypersensitive in fetal liver nuclei of these expressing transgenic lines. Taken together, these results demonstrate that LCR activity is the culmination of at least two separable functions including: (i) a novel activity located in 5′HS3 that dominantly opens and remodels chromatin structure; and (ii) a recessive enhancer activity residing in 5′HS2. We postulate that the different elements of the LCR form a 'holocomplex' that interacts with the individual globin genes.en_HK
dc.format.extent418 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emboj/index.htmlen_HK
dc.relation.ispartofEMBO Journalen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectβ-globinen_HK
dc.subjectChromatinen_HK
dc.subjectLocus control regionen_HK
dc.subject.meshBase Sequence-
dc.subject.meshChromatin - genetics-
dc.subject.meshChromosome Mapping-
dc.subject.meshDNA Primers - genetics-
dc.subject.meshGlobins - genetics-
dc.titleA dominant chromatin-opening activity in 5 hypersensitive site 3 of the human β-globin locus control regionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0261-4189&volume=15&issue=3&spage=562&epage=568&date=1996&atitle=A+dominant+chromatin-opening+activity+in+5%27+hypersensitive+site+3+of+the+human+β-globin+locus+control+regionen_HK
dc.identifier.emailTan-Un, KC: kctanun@hkucc.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid8599939-
dc.identifier.pmcidPMC449974-
dc.identifier.scopuseid_2-s2.0-0030050402en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030050402&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue3en_HK
dc.identifier.spage562en_HK
dc.identifier.epage568en_HK
dc.identifier.isiWOS:A1996TU92500012-
dc.publisher.placeUnited Kingdomen_HK

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