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Article: The rabbit sex hormone-binding globulin gene: Structural organization and characterization of its 5′-flanking region

TitleThe rabbit sex hormone-binding globulin gene: Structural organization and characterization of its 5′-flanking region
Authors
Issue Date2000
PublisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.org
Citation
Endocrinology, 2000, v. 141 n. 4, p. 1356-1365 How to Cite?
AbstractSex hormone-binding globulin (SHBG) transports sex steroids in the blood. In humans and rabbits, the gene encoding SHBG (shbg) is expressed primarily in the liver and testis, whereas the testis is the major site of shbg expression in rodents postnatally. Sequence analysis has revealed that rabbit shbg (rbshbg) spans 2.5 kb and comprises eight exons with consensus splice sites at all exon-intron junctions. The major transcription start site of rbshbg is located 52 bp upstream from the translation initiation codon for the rabbit SHBG precursor. Unlike the situation in humans and rats, rbshbg transcripts contain no alternative exon 1 sequences in the liver or testis, and this suggests that the rbshbg 5′-flanking region plays an equally important role in controlling transcription of this gene in these tissues. Like the human and rat shbg promoter sequences, the rbshbg proximal promoter lacks a typical TATA box. It also contains several transcription factor-binding sites, but deoxyribonuclease I footprinting experiments indicated that the human and rabbit shbg proximal promoters interact quite differently with proteins extracted from rabbit liver nuclei. However, the predominant footprint on the rbshbg promoter is conserved at the same position within the human shbg (hshbg) promoter and includes consensus binding sites for the transcription factor nuclear factor-1. Transient transfection studies of the rbshbg 5′-flanking sequence (893 bp) revealed regions that actively enhance and repress its activity in human hepatoblastoma and mouse Sertoli cells, but not in Chinese hamster ovary cells. Like the rat shbg proximal promoter, the rbshbg 5′-flanking sequence lacks a region that corresponds to a cis-element, designated footprinted region 4 in the hshbg proximal promoter. Furthermore, the hshbg promoter footprinted region 3 sequence is poorly conserved in rbshbg, and when mutated to resemble the corresponding human sequence it increased the transcriptional activity of the rbshbg promoter by 7-fold in hepatoblastoma cells. Thus, the rabbit and hshbg promoters appear to be controlled by a different set of transcriptional regulators. Further comparisons of their functional activities may shed light on species-specific differences in the spatial and temporal expression of this gene, the products of which play important roles in regulating sex steroid access to target cells.
Persistent Identifierhttp://hdl.handle.net/10722/178716
ISSN
2015 Impact Factor: 4.159
2015 SCImago Journal Rankings: 2.363
References

 

DC FieldValueLanguage
dc.contributor.authorIp, YCen_US
dc.contributor.authorLee, WMen_US
dc.contributor.authorHammond, GLen_US
dc.date.accessioned2012-12-19T09:49:18Z-
dc.date.available2012-12-19T09:49:18Z-
dc.date.issued2000en_US
dc.identifier.citationEndocrinology, 2000, v. 141 n. 4, p. 1356-1365en_US
dc.identifier.issn0013-7227en_US
dc.identifier.urihttp://hdl.handle.net/10722/178716-
dc.description.abstractSex hormone-binding globulin (SHBG) transports sex steroids in the blood. In humans and rabbits, the gene encoding SHBG (shbg) is expressed primarily in the liver and testis, whereas the testis is the major site of shbg expression in rodents postnatally. Sequence analysis has revealed that rabbit shbg (rbshbg) spans 2.5 kb and comprises eight exons with consensus splice sites at all exon-intron junctions. The major transcription start site of rbshbg is located 52 bp upstream from the translation initiation codon for the rabbit SHBG precursor. Unlike the situation in humans and rats, rbshbg transcripts contain no alternative exon 1 sequences in the liver or testis, and this suggests that the rbshbg 5′-flanking region plays an equally important role in controlling transcription of this gene in these tissues. Like the human and rat shbg promoter sequences, the rbshbg proximal promoter lacks a typical TATA box. It also contains several transcription factor-binding sites, but deoxyribonuclease I footprinting experiments indicated that the human and rabbit shbg proximal promoters interact quite differently with proteins extracted from rabbit liver nuclei. However, the predominant footprint on the rbshbg promoter is conserved at the same position within the human shbg (hshbg) promoter and includes consensus binding sites for the transcription factor nuclear factor-1. Transient transfection studies of the rbshbg 5′-flanking sequence (893 bp) revealed regions that actively enhance and repress its activity in human hepatoblastoma and mouse Sertoli cells, but not in Chinese hamster ovary cells. Like the rat shbg proximal promoter, the rbshbg 5′-flanking sequence lacks a region that corresponds to a cis-element, designated footprinted region 4 in the hshbg proximal promoter. Furthermore, the hshbg promoter footprinted region 3 sequence is poorly conserved in rbshbg, and when mutated to resemble the corresponding human sequence it increased the transcriptional activity of the rbshbg promoter by 7-fold in hepatoblastoma cells. Thus, the rabbit and hshbg promoters appear to be controlled by a different set of transcriptional regulators. Further comparisons of their functional activities may shed light on species-specific differences in the spatial and temporal expression of this gene, the products of which play important roles in regulating sex steroid access to target cells.en_US
dc.languageengen_US
dc.publisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.orgen_US
dc.relation.ispartofEndocrinologyen_US
dc.rightsEndocrinology. Copyright © The Endocrine Society.-
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequence - Geneticsen_US
dc.subject.meshCho Cellsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCricetinaeen_US
dc.subject.meshHumansen_US
dc.subject.meshLiver - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNuclear Proteins - Physiologyen_US
dc.subject.meshRabbitsen_US
dc.subject.meshRatsen_US
dc.subject.meshSex Hormone-Binding Globulin - Genetics - Physiologyen_US
dc.subject.meshTranscription, Geneticen_US
dc.titleThe rabbit sex hormone-binding globulin gene: Structural organization and characterization of its 5′-flanking regionen_US
dc.typeArticleen_US
dc.identifier.emailLee, WM: hrszlwm@hku.hken_US
dc.identifier.authorityLee, WM=rp00728en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1210/endo.141.4.7406en_US
dc.identifier.pmid10746639-
dc.identifier.scopuseid_2-s2.0-0034458389en_US
dc.identifier.hkuros48608-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034458389&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume141en_US
dc.identifier.issue4en_US
dc.identifier.spage1356en_US
dc.identifier.epage1365en_US
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridIp, YC=55201057600en_US
dc.identifier.scopusauthoridLee, WM=24799156600en_US
dc.identifier.scopusauthoridHammond, GL=7202011645en_US

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