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Article: Hoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning

TitleHoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning
Authors
KeywordsFacial branchiomotor neurons
Hindbrain patterning
Hox gene regulation
Hoxb1
Hoxb3
Neurogenesis
Neuronal identity
Posterior prevalence
Rhombomere 4
Issue Date2011
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbio
Citation
Developmental Biology, 2011, v. 352 n. 2, p. 382-392 How to Cite?
AbstractThe spatial regulation of combinatorial expression of Hox genes is critical for determining hindbrain rhombomere (r) identities. To address the cross-regulatory relationship between Hox genes in hindbrain neuronal specification, we have generated a gain-of-function transgenic mouse mutant Hoxb3 Tg using the Hoxb2 r4-specific enhancer element. Interestingly, in r4 of the Hoxb3 Tg mutant where Hoxb3 was ectopically expressed, the expression of Hoxb1 was specifically abolished. The hindbrain neuronal defects of the Hoxb3 Tg mutant mice were similar to those of Hoxb1 -/- mutants. Therefore, we hypothesized that Hoxb3 could directly suppress Hoxb1 expression. We first identified a novel Hoxb3 binding site S3 on the Hoxb1 locus and confirmed protein binding to this site by EMSA, and by in vivo ChIP analysis using P19 cells and hindbrain tissues from the Hoxb3 Tg mutant. We further showed that Hoxb3 could suppress Hoxb1 transcriptional activity by chick in ovo luciferase reporter assay. Moreover, in E10.5 wildtype caudal hindbrain, where Hoxb1 is not expressed, we showed by in vivo ChIP that Hoxb3 was consistently bound to the S3 site on the Hoxb1 gene. This study reveals a novel negative regulatory mechanism by which Hoxb3 as a posterior gene serves to restrict Hoxb1 expression in r4 by direct transcriptional repression to maintain the rhombomere identity. © 2011 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/147630
ISSN
2015 Impact Factor: 3.155
2015 SCImago Journal Rankings: 2.554
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU7294/98M
HKU2/01C
HKU4/05C
HKU775209M
Funding Information:

We thank Dr. Nancy Manley for the Hoxb3-/- knockout mice; Ms. S.L. Tsang, Dr. Keith Leung and the Transgenic Core Facility for technical support and animal husbandry; and Drs. Martin Cheung and L.A. Osorio Da Silva for assistance in chick in ovo electroporation experiments. This work was supported by research grants from the Hong Kong Research Grants Council (HKU7294/98M, HKU2/01C, HKU4/05C, HKU775209M).

References

 

DC FieldValueLanguage
dc.contributor.authorWong, EYMen_HK
dc.contributor.authorWang, XAen_HK
dc.contributor.authorMak, SSen_HK
dc.contributor.authorSaePang, JJen_HK
dc.contributor.authorLing, KWen_HK
dc.contributor.authorFritzsch, Ben_HK
dc.contributor.authorSham, MHen_HK
dc.date.accessioned2012-05-29T06:05:06Z-
dc.date.available2012-05-29T06:05:06Z-
dc.date.issued2011en_HK
dc.identifier.citationDevelopmental Biology, 2011, v. 352 n. 2, p. 382-392en_HK
dc.identifier.issn0012-1606en_HK
dc.identifier.urihttp://hdl.handle.net/10722/147630-
dc.description.abstractThe spatial regulation of combinatorial expression of Hox genes is critical for determining hindbrain rhombomere (r) identities. To address the cross-regulatory relationship between Hox genes in hindbrain neuronal specification, we have generated a gain-of-function transgenic mouse mutant Hoxb3 Tg using the Hoxb2 r4-specific enhancer element. Interestingly, in r4 of the Hoxb3 Tg mutant where Hoxb3 was ectopically expressed, the expression of Hoxb1 was specifically abolished. The hindbrain neuronal defects of the Hoxb3 Tg mutant mice were similar to those of Hoxb1 -/- mutants. Therefore, we hypothesized that Hoxb3 could directly suppress Hoxb1 expression. We first identified a novel Hoxb3 binding site S3 on the Hoxb1 locus and confirmed protein binding to this site by EMSA, and by in vivo ChIP analysis using P19 cells and hindbrain tissues from the Hoxb3 Tg mutant. We further showed that Hoxb3 could suppress Hoxb1 transcriptional activity by chick in ovo luciferase reporter assay. Moreover, in E10.5 wildtype caudal hindbrain, where Hoxb1 is not expressed, we showed by in vivo ChIP that Hoxb3 was consistently bound to the S3 site on the Hoxb1 gene. This study reveals a novel negative regulatory mechanism by which Hoxb3 as a posterior gene serves to restrict Hoxb1 expression in r4 by direct transcriptional repression to maintain the rhombomere identity. © 2011 Elsevier Inc.en_HK
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbioen_HK
dc.relation.ispartofDevelopmental Biologyen_HK
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Developmental Biology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Developmental Biology, 2011, v. 352 n. 2, p. 382-392. DOI: 10.1016/j.ydbio.2011.02.003-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectFacial branchiomotor neuronsen_HK
dc.subjectHindbrain patterningen_HK
dc.subjectHox gene regulationen_HK
dc.subjectHoxb1en_HK
dc.subjectHoxb3en_HK
dc.subjectNeurogenesisen_HK
dc.subjectNeuronal identityen_HK
dc.subjectPosterior prevalenceen_HK
dc.subjectRhombomere 4en_HK
dc.subject.meshAnimalsen_US
dc.subject.meshAnimals, Genetically Modifieden_US
dc.subject.meshAvian Proteins - Genetics - Metabolismen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBinding Sites - Geneticsen_US
dc.subject.meshBody Patterningen_US
dc.subject.meshChick Embryoen_US
dc.subject.meshCraniofacial Abnormalities - Embryology - Genetics - Metabolismen_US
dc.subject.meshDna Primers - Geneticsen_US
dc.subject.meshGene Expression Regulation, Developmentalen_US
dc.subject.meshHomeodomain Proteins - Genetics - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Mutant Strainsen_US
dc.subject.meshMice, Transgenicen_US
dc.subject.meshModels, Neurologicalen_US
dc.subject.meshNeurogenesis - Genetics - Physiologyen_US
dc.subject.meshRhombencephalon - Embryology - Metabolismen_US
dc.titleHoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterningen_HK
dc.typeArticleen_HK
dc.identifier.emailWong, EYM: elainewg@hku.hken_HK
dc.identifier.emailSham, MH: mhsham@hku.hken_HK
dc.identifier.authorityWong, EYM=rp01718en_HK
dc.identifier.authoritySham, MH=rp00380en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1016/j.ydbio.2011.02.003en_HK
dc.identifier.pmid21320481-
dc.identifier.scopuseid_2-s2.0-79953025098en_HK
dc.identifier.hkuros190257-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79953025098&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume352en_HK
dc.identifier.issue2en_HK
dc.identifier.spage382en_HK
dc.identifier.epage392en_HK
dc.identifier.eissn1095-564X-
dc.identifier.isiWOS:000289180200018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWong, EYM=36719382700en_HK
dc.identifier.scopusauthoridWang, XA=39561647100en_HK
dc.identifier.scopusauthoridMak, SS=11840299400en_HK
dc.identifier.scopusauthoridSaePang, JJ=36993274900en_HK
dc.identifier.scopusauthoridLing, KW=39561283000en_HK
dc.identifier.scopusauthoridFritzsch, B=7006714975en_HK
dc.identifier.scopusauthoridSham, MH=7003729109en_HK
dc.identifier.citeulike8836299-

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