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Article: Segmental expression of Hoxa-2 in the hindbrain is directly regulated by Krox-20

TitleSegmental expression of Hoxa-2 in the hindbrain is directly regulated by Krox-20
Authors
Issue Date1996
PublisherThe Company of Biologists Ltd. The Journal's web site is located at http://dev.biologists.org
Citation
Development, 1996, v. 122 n. 2, p. 543-554 How to Cite?
AbstractThe hindbrain is a segmented structure divided into repeating metameric units termed rhombomeres (r). The Hox family, vertebrate homologs of the Drosophila HOM-C homeotic selector genes, are expressed in rhombomere-restricted patterns and are believed to participate in regulating segmental identities. Krox-20, a zinc finger gene, has a highly conserved pattern of expression in r3 and r5 and is functionally required for their maintenance in mouse embryos. Krox-20 has been shown to directly regulate the Hoxb-2 gene and we wanted to determine if it was involved in regulating multiple Hox genes as a part of its functional role. Hoxa-2 is the only known paralog of Hoxb-2, and we examined the patterns of expression of the mouse Hoxa-2 gene with particular focus on r3 and r5 in wild type and Krox-20(-/-) mutant embryos. There was a clear loss of expression in r3, which indicated that Hoxa-2 was downstream of Krox-20. Using transgenic analysis with E. coli lacZ reporter genes we have identified and mapped an r3/r5 enhancer in the 5' flanking region of the Hoxa-2 gene. Deletion analysis narrowed this region to an 809 bp BglII fragment, and in vitro binding and competition assays with bacterially expressed Krox-20 protein identified two sites within the enhancer. Mutation of these Krox-20 sites in the regulatory region specifically abolished r3/r5 activity, but did not affect neural crest and mesodermal components. This indicated that the two Krox-20 sites are required in vivo for enhancer function. Furthermore, ectopic expression of Krox-20 in r4 was able to transactivate the Hoxa-2/lacZ reporter in this rhombomere. Together our findings suggest that Krox-20 directly participates in the transcriptional regulation of Hoxa-2 during hindbrain segmentation, and is responsible for the upregulation of the r3 and r5 domains of expression of both vertebrate group 2 Hox paralogs. Therefore, the segmental phenotypes in the Krox-20 mutants are likely to reflect the role of Krox-20 in directly regulating multiple Hox genes.
Persistent Identifierhttp://hdl.handle.net/10722/147502
ISSN
2015 Impact Factor: 6.059
2015 SCImago Journal Rankings: 5.239
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorNonchev, Sen_US
dc.contributor.authorVesque, Cen_US
dc.contributor.authorMaconochie, Men_US
dc.contributor.authorSeitanidou, Ten_US
dc.contributor.authorArizaMcnaughton, Len_US
dc.contributor.authorFrain, Men_US
dc.contributor.authorMarshall, Hen_US
dc.contributor.authorSham, MHen_US
dc.contributor.authorKrumlauf, Ren_US
dc.contributor.authorCharnay, Pen_US
dc.date.accessioned2012-05-29T06:04:11Z-
dc.date.available2012-05-29T06:04:11Z-
dc.date.issued1996en_US
dc.identifier.citationDevelopment, 1996, v. 122 n. 2, p. 543-554en_US
dc.identifier.issn0950-1991en_US
dc.identifier.urihttp://hdl.handle.net/10722/147502-
dc.description.abstractThe hindbrain is a segmented structure divided into repeating metameric units termed rhombomeres (r). The Hox family, vertebrate homologs of the Drosophila HOM-C homeotic selector genes, are expressed in rhombomere-restricted patterns and are believed to participate in regulating segmental identities. Krox-20, a zinc finger gene, has a highly conserved pattern of expression in r3 and r5 and is functionally required for their maintenance in mouse embryos. Krox-20 has been shown to directly regulate the Hoxb-2 gene and we wanted to determine if it was involved in regulating multiple Hox genes as a part of its functional role. Hoxa-2 is the only known paralog of Hoxb-2, and we examined the patterns of expression of the mouse Hoxa-2 gene with particular focus on r3 and r5 in wild type and Krox-20(-/-) mutant embryos. There was a clear loss of expression in r3, which indicated that Hoxa-2 was downstream of Krox-20. Using transgenic analysis with E. coli lacZ reporter genes we have identified and mapped an r3/r5 enhancer in the 5' flanking region of the Hoxa-2 gene. Deletion analysis narrowed this region to an 809 bp BglII fragment, and in vitro binding and competition assays with bacterially expressed Krox-20 protein identified two sites within the enhancer. Mutation of these Krox-20 sites in the regulatory region specifically abolished r3/r5 activity, but did not affect neural crest and mesodermal components. This indicated that the two Krox-20 sites are required in vivo for enhancer function. Furthermore, ectopic expression of Krox-20 in r4 was able to transactivate the Hoxa-2/lacZ reporter in this rhombomere. Together our findings suggest that Krox-20 directly participates in the transcriptional regulation of Hoxa-2 during hindbrain segmentation, and is responsible for the upregulation of the r3 and r5 domains of expression of both vertebrate group 2 Hox paralogs. Therefore, the segmental phenotypes in the Krox-20 mutants are likely to reflect the role of Krox-20 in directly regulating multiple Hox genes.en_US
dc.languageengen_US
dc.publisherThe Company of Biologists Ltd. The Journal's web site is located at http://dev.biologists.org-
dc.relation.ispartofDevelopmenten_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshConserved Sequenceen_US
dc.subject.meshDna-Binding Proteins - Biosynthesis - Metabolismen_US
dc.subject.meshEarly Growth Response Protein 2en_US
dc.subject.meshEnhancer Elements, Geneticen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshGenes, Homeoboxen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNerve Tissue Proteins - Biosynthesisen_US
dc.subject.meshOligonucleotide Probesen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshRecombinant Proteins - Analysis - Biosynthesisen_US
dc.subject.meshRestriction Mappingen_US
dc.subject.meshRhombencephalon - Cytology - Embryology - Metabolismen_US
dc.subject.meshTranscription Factors - Biosynthesis - Metabolismen_US
dc.subject.meshVertebratesen_US
dc.subject.meshZinc Fingersen_US
dc.subject.meshBeta-Galactosidase - Analysis - Biosynthesisen_US
dc.titleSegmental expression of Hoxa-2 in the hindbrain is directly regulated by Krox-20en_US
dc.typeArticleen_US
dc.identifier.emailSham, MH:mhsham@hkucc.hku.hken_US
dc.identifier.authoritySham, MH=rp00380en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid8625806-
dc.identifier.scopuseid_2-s2.0-13344278018en_US
dc.identifier.hkuros15574-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-13344278018&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume122en_US
dc.identifier.issue2en_US
dc.identifier.spage543en_US
dc.identifier.epage554en_US
dc.identifier.isiWOS:A1996TY51700015-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridNonchev, S=6603818489en_US
dc.identifier.scopusauthoridVesque, C=6603365734en_US
dc.identifier.scopusauthoridMaconochie, M=8780581500en_US
dc.identifier.scopusauthoridSeitanidou, T=6603657119en_US
dc.identifier.scopusauthoridArizaMcNaughton, L=6601980638en_US
dc.identifier.scopusauthoridFrain, M=6603843656en_US
dc.identifier.scopusauthoridMarshall, H=7102515675en_US
dc.identifier.scopusauthoridSham, MH=7003729109en_US
dc.identifier.scopusauthoridKrumlauf, R=7006242495en_US
dc.identifier.scopusauthoridCharnay, P=7004489856en_US

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