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Article: Regulatory analysis of the mouse Hoxb3 gene: Multiple elements work in concert to direct temporal and spatial patterns of expression

TitleRegulatory analysis of the mouse Hoxb3 gene: Multiple elements work in concert to direct temporal and spatial patterns of expression
Authors
Issue Date2001
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbio
Citation
Developmental Biology, 2001, v. 232 n. 1, p. 176-190 How to Cite?
AbstractThe expression pattern of the mouse Hoxb3 gene is exceptionally complex and dynamic compared with that of other members of the Hoxb cluster. There are multiple types of transcripts for Hoxb3 gene, and the anterior boundaries of its expression vary at different stages of development. Two enhancers flanking Hoxb3 on the 3′ and 5′ sides regulate Hoxb2 and Hoxb4, respectively, and these control regions define the two ends of a 28-kb interval in and around the Hoxb3 locus. To assay the regulatory potential of DNA fragments in this interval we have used transgenic analysis with a lacZ reporter gene to locate cis-elements for directing the dynamic patterns of Hoxb3 expression. Our detailed analysis has identified four new and widely spaced cis-acting regulatory regions that can together account for major aspects of the Hoxb3 expression pattern. Elements Ib, IIIa, and IVb control gene expression in neural and mesodermal tissues; element Va controls mesoderm-specific gene expression. The most anterior neural expression domain of Hoxb3 is controlled by an r5 enhancer (element IVa); element IIIa directs reporter expression in the anterior spinal cord and hindbrain up to r6, and the region A enhancer (in element I) mediates posterior neural expression. Hence, the regulation of segmental expression of Hoxb3 in the hindbrain is different from that of Hoxa3, as two separate enhancer elements contribute to expression in r5 and r6. The mesoderm-specific element (Va) directs reporter expression to prevertebra C1 at 12.5 dpc, which is the anterior limit of paraxial mesoderm expression for Hoxb3. When tested in combinations, these cis-elements appear to work as modules in an additive manner to recapitulate the major endogenous expression patterns of Hoxb3 during embryogenesis. Together our study shows that multiple control elements direct reporter gene expression in diverse tissue-, temporal-, and spatially restricted subset of the endogenous Hoxb3 expression domains and work in concert to control the neural and mesodermal patterns of expression. © 2001 Academic Press.
Persistent Identifierhttp://hdl.handle.net/10722/68190
ISSN
2015 Impact Factor: 3.155
2015 SCImago Journal Rankings: 2.554
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKwan, CTen_HK
dc.contributor.authorTsang, SLen_HK
dc.contributor.authorKrumlauf, Ren_HK
dc.contributor.authorSham, MHen_HK
dc.date.accessioned2010-09-06T06:02:13Z-
dc.date.available2010-09-06T06:02:13Z-
dc.date.issued2001en_HK
dc.identifier.citationDevelopmental Biology, 2001, v. 232 n. 1, p. 176-190en_HK
dc.identifier.issn0012-1606en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68190-
dc.description.abstractThe expression pattern of the mouse Hoxb3 gene is exceptionally complex and dynamic compared with that of other members of the Hoxb cluster. There are multiple types of transcripts for Hoxb3 gene, and the anterior boundaries of its expression vary at different stages of development. Two enhancers flanking Hoxb3 on the 3′ and 5′ sides regulate Hoxb2 and Hoxb4, respectively, and these control regions define the two ends of a 28-kb interval in and around the Hoxb3 locus. To assay the regulatory potential of DNA fragments in this interval we have used transgenic analysis with a lacZ reporter gene to locate cis-elements for directing the dynamic patterns of Hoxb3 expression. Our detailed analysis has identified four new and widely spaced cis-acting regulatory regions that can together account for major aspects of the Hoxb3 expression pattern. Elements Ib, IIIa, and IVb control gene expression in neural and mesodermal tissues; element Va controls mesoderm-specific gene expression. The most anterior neural expression domain of Hoxb3 is controlled by an r5 enhancer (element IVa); element IIIa directs reporter expression in the anterior spinal cord and hindbrain up to r6, and the region A enhancer (in element I) mediates posterior neural expression. Hence, the regulation of segmental expression of Hoxb3 in the hindbrain is different from that of Hoxa3, as two separate enhancer elements contribute to expression in r5 and r6. The mesoderm-specific element (Va) directs reporter expression to prevertebra C1 at 12.5 dpc, which is the anterior limit of paraxial mesoderm expression for Hoxb3. When tested in combinations, these cis-elements appear to work as modules in an additive manner to recapitulate the major endogenous expression patterns of Hoxb3 during embryogenesis. Together our study shows that multiple control elements direct reporter gene expression in diverse tissue-, temporal-, and spatially restricted subset of the endogenous Hoxb3 expression domains and work in concert to control the neural and mesodermal patterns of expression. © 2001 Academic Press.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbioen_HK
dc.relation.ispartofDevelopmental Biologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshGene Expression Regulation, Developmentalen_HK
dc.subject.meshHomeodomain Proteins - geneticsen_HK
dc.subject.meshMesoderm - metabolismen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMice, Inbred CBAen_HK
dc.subject.meshMice, Transgenicen_HK
dc.subject.meshXenopus Proteinsen_HK
dc.titleRegulatory analysis of the mouse Hoxb3 gene: Multiple elements work in concert to direct temporal and spatial patterns of expressionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0012-1606&volume=232&issue=1&spage=176&epage=190&date=2001&atitle=Regulatory+analysis+of+the+mouse+Hoxb3+gene:+Multiple+elements+work+in+concert+to+direct+temporal+and+spatial+patterns+of+expressionen_HK
dc.identifier.emailSham, MH:mhsham@hkucc.hku.hken_HK
dc.identifier.authoritySham, MH=rp00380en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1006/dbio.2001.0157en_HK
dc.identifier.pmid11254356-
dc.identifier.scopuseid_2-s2.0-0035313081en_HK
dc.identifier.hkuros58624en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035313081&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume232en_HK
dc.identifier.issue1en_HK
dc.identifier.spage176en_HK
dc.identifier.epage190en_HK
dc.identifier.isiWOS:000167837000010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKwan, CT=7201421142en_HK
dc.identifier.scopusauthoridTsang, SL=15722984500en_HK
dc.identifier.scopusauthoridKrumlauf, R=7006242495en_HK
dc.identifier.scopusauthoridSham, MH=7003729109en_HK

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