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Article: Gamma-interferon activates a nuclear protein that binds to the gamma- interferon activation site of the thyroglobulin gene

TitleGamma-interferon activates a nuclear protein that binds to the gamma- interferon activation site of the thyroglobulin gene
Authors
Issue Date1998
PublisherSociety for Endocrinology. The Journal's web site is located at http://jme.endocrinology-journals.org/
Citation
Journal Of Molecular Endocrinology, 1998, v. 20 n. 3, p. 293-298 How to Cite?
AbstractThe release of interferon-gamma (IFNγ) has been demonstrated from the infiltrating T lymphocytes of the thyroid gland from patients with autoimmune thyroid disease (AITD). We have shown previously that IFNγ inhibited thyroglobulin (Tg) gene transcription, and that its action was mediated by an increase in intracellular calcium and inositol phosphates. In the present study, we tried to determine the specific site of action of IFNγ on the Tg gene. A 565 bp fragment (position -530 to +34) spanning the transcriptional start site of the human Tg promoter was ligated to the luciferase plasmid and transiently transfected into human thyrocytes. Stimulation with TSH (10 mlU/l) and IFNγ (500 IU/l) resulted in a twofold increase and a 60% reduction in the luciferase activity respectively, similar to the effect observed with the endogenous Tg gene. Deletion studies revealed that the region with the strongest suppression by IFNγ lay between 5' -388 to -258. Mobility gel shift experiments and DNA footprinting experiments demonstrated that the action of IFNγ was mediated through a trans-acting protein which complexed to position - 282 to - 262 TTGAGCCTGTTCCCTC CAAA. Position -272 to -261 TTCCCTCCAA corresponded to the gamma-interferon activation site (GAS) consensus sequence TTNC(C)(T) NNNAA. The turnover time of the nuclear protein lasted for only 4 h although the suppressive effect of IFNγ on Tg gene transcription lasted for 48 h. The effect of IFNγ was lost when the thyrocytes were co-treated with genistein, a specific tyrosine kinase inhibitor. The presence of the GAS in the promoter sequence of the Tg gene confirms the specific action of IFNγ in thyroid hormone metabolism. In conclusion, apart from its regulatory role in W cell development and perpetuation of the immune response in AITD, IFNγ may also play a role in altering cellular function of the thyrocytes by its action on the Tg gene promoter.
Persistent Identifierhttp://hdl.handle.net/10722/49076
ISSN
2015 Impact Factor: 2.947
2015 SCImago Journal Rankings: 1.674
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKung, AWCen_HK
dc.contributor.authorLau, KSen_HK
dc.date.accessioned2008-06-12T06:33:53Z-
dc.date.available2008-06-12T06:33:53Z-
dc.date.issued1998en_HK
dc.identifier.citationJournal Of Molecular Endocrinology, 1998, v. 20 n. 3, p. 293-298en_HK
dc.identifier.issn0952-5041en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49076-
dc.description.abstractThe release of interferon-gamma (IFNγ) has been demonstrated from the infiltrating T lymphocytes of the thyroid gland from patients with autoimmune thyroid disease (AITD). We have shown previously that IFNγ inhibited thyroglobulin (Tg) gene transcription, and that its action was mediated by an increase in intracellular calcium and inositol phosphates. In the present study, we tried to determine the specific site of action of IFNγ on the Tg gene. A 565 bp fragment (position -530 to +34) spanning the transcriptional start site of the human Tg promoter was ligated to the luciferase plasmid and transiently transfected into human thyrocytes. Stimulation with TSH (10 mlU/l) and IFNγ (500 IU/l) resulted in a twofold increase and a 60% reduction in the luciferase activity respectively, similar to the effect observed with the endogenous Tg gene. Deletion studies revealed that the region with the strongest suppression by IFNγ lay between 5' -388 to -258. Mobility gel shift experiments and DNA footprinting experiments demonstrated that the action of IFNγ was mediated through a trans-acting protein which complexed to position - 282 to - 262 TTGAGCCTGTTCCCTC CAAA. Position -272 to -261 TTCCCTCCAA corresponded to the gamma-interferon activation site (GAS) consensus sequence TTNC(C)(T) NNNAA. The turnover time of the nuclear protein lasted for only 4 h although the suppressive effect of IFNγ on Tg gene transcription lasted for 48 h. The effect of IFNγ was lost when the thyrocytes were co-treated with genistein, a specific tyrosine kinase inhibitor. The presence of the GAS in the promoter sequence of the Tg gene confirms the specific action of IFNγ in thyroid hormone metabolism. In conclusion, apart from its regulatory role in W cell development and perpetuation of the immune response in AITD, IFNγ may also play a role in altering cellular function of the thyrocytes by its action on the Tg gene promoter.en_HK
dc.format.extent418 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherSociety for Endocrinology. The Journal's web site is located at http://jme.endocrinology-journals.org/en_HK
dc.relation.ispartofJournal of Molecular Endocrinologyen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsDisclaimer. This is not the definitive version of record of this article. This manuscript has been accepted for publication in Journal of Molecular Endocrinology, but the version presented here has not yet been copy edited, formatted or proofed. Consequently, the Society for Endocrinology accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at http://dx.doi.org/10.1677/jme.0.0200293. © 1998 Society for Endocrinologyen_HK
dc.subject.meshMedical sciencesen_HK
dc.subject.meshEndocrinologyen_HK
dc.titleGamma-interferon activates a nuclear protein that binds to the gamma- interferon activation site of the thyroglobulin geneen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0952-5041&volume=20&issue=3&spage=293&epage=298&date=1998&atitle=Gamma-interferon+activates+a+nuclear+protein+that+binds+to+the+gamma-interferon+activation+site+of+the+thyroglobulin+geneen_HK
dc.identifier.emailKung, AWC:awckung@hku.hken_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1677/jme.0.0200293en_HK
dc.identifier.pmid9687151-
dc.identifier.scopuseid_2-s2.0-0031808882en_HK
dc.identifier.hkuros33945-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0031808882&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume20en_HK
dc.identifier.issue3en_HK
dc.identifier.spage293en_HK
dc.identifier.epage298en_HK
dc.identifier.isiWOS:000074377200001-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridKung, AWC=7102322339en_HK
dc.identifier.scopusauthoridLau, KS=35205833900en_HK

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