Characterization of thyroid hormone response elements in the gene for chicken malic enzyme. Factors that influence triiodothyronine responsiveness

Debbie C. Thurmond, Alan G. Goodridge

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Transcription of the gene for malic enzyme in chick embryo hepatocytes is stimulated about 30-fold by triiodothyronine (T3). T3 responsiveness is mediated by seven direct repeat hexamers that resemble T3 response elements (T3REs); these elements are located far up-stream in the 5'-flanking DNA (Hodnett, D. W., Fantozzzi, D. A., Thurmond, D.C., Klautky, S. A., MacPhee, K. G., Estrem, S. T., Xu, G., and Goodridge, A. G. (1996) Arch. Biochem. Biophys. 334, 309-324). In transiently transfected hepatocytes, single copies of six of these elements conferred varying degrees of T3 responsiveness to linked reporter genes. In gel electrophoretic mobility shift analyses, the T3REs bound retinoid X receptor (RXR)-T3 receptor (TR) heterodimers and non- RXR/TR factors present in nuclear extracts prepared from hepatocytes. Binding of the non-RXP/TR factors was specific to individual T3REs and was unaffected by antibodies to TR or RXR. Mutagenesis of binding sites for proteins specific for T3REs 2-5 altered binding of the proteins and T3 responsiveness. These factors appear to bind to and alter function of T3REs without binding directly to TR, differentiating their actions from other TR cofactors; they were tentatively characterized as co-repressers, inhibitors, and activators of T3RE function. Together with RXR and TR, they modulate T3 responsiveness of the gene for chicken malic enzyme.

Original languageEnglish (US)
Pages (from-to)1613-1622
Number of pages10
JournalJournal of Biological Chemistry
Volume273
Issue number3
DOIs
StatePublished - Jan 16 1998
Externally publishedYes

Fingerprint

Thyroid Hormone Receptors
Response Elements
Triiodothyronine
Thyroid Hormones
Chickens
Genes
Retinoid X Receptors
Enzymes
Hepatocytes
Carrier Proteins
Electrophoretic mobility
Mutagenesis
Nucleic Acid Repetitive Sequences
Arches
Chick Embryo
Transcription
Reporter Genes
Gels
Binding Sites
Antibodies

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of thyroid hormone response elements in the gene for chicken malic enzyme. Factors that influence triiodothyronine responsiveness. / Thurmond, Debbie C.; Goodridge, Alan G.

In: Journal of Biological Chemistry, Vol. 273, No. 3, 16.01.1998, p. 1613-1622.

Research output: Contribution to journalArticle

@article{efb1a2fbf0134ceda6767a3b0ca2d548,
title = "Characterization of thyroid hormone response elements in the gene for chicken malic enzyme. Factors that influence triiodothyronine responsiveness",
abstract = "Transcription of the gene for malic enzyme in chick embryo hepatocytes is stimulated about 30-fold by triiodothyronine (T3). T3 responsiveness is mediated by seven direct repeat hexamers that resemble T3 response elements (T3REs); these elements are located far up-stream in the 5'-flanking DNA (Hodnett, D. W., Fantozzzi, D. A., Thurmond, D.C., Klautky, S. A., MacPhee, K. G., Estrem, S. T., Xu, G., and Goodridge, A. G. (1996) Arch. Biochem. Biophys. 334, 309-324). In transiently transfected hepatocytes, single copies of six of these elements conferred varying degrees of T3 responsiveness to linked reporter genes. In gel electrophoretic mobility shift analyses, the T3REs bound retinoid X receptor (RXR)-T3 receptor (TR) heterodimers and non- RXR/TR factors present in nuclear extracts prepared from hepatocytes. Binding of the non-RXP/TR factors was specific to individual T3REs and was unaffected by antibodies to TR or RXR. Mutagenesis of binding sites for proteins specific for T3REs 2-5 altered binding of the proteins and T3 responsiveness. These factors appear to bind to and alter function of T3REs without binding directly to TR, differentiating their actions from other TR cofactors; they were tentatively characterized as co-repressers, inhibitors, and activators of T3RE function. Together with RXR and TR, they modulate T3 responsiveness of the gene for chicken malic enzyme.",
author = "Thurmond, {Debbie C.} and Goodridge, {Alan G.}",
year = "1998",
month = "1",
day = "16",
doi = "10.1074/jbc.273.3.1613",
language = "English (US)",
volume = "273",
pages = "1613--1622",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "3",

}

TY - JOUR

T1 - Characterization of thyroid hormone response elements in the gene for chicken malic enzyme. Factors that influence triiodothyronine responsiveness

AU - Thurmond, Debbie C.

AU - Goodridge, Alan G.

PY - 1998/1/16

Y1 - 1998/1/16

N2 - Transcription of the gene for malic enzyme in chick embryo hepatocytes is stimulated about 30-fold by triiodothyronine (T3). T3 responsiveness is mediated by seven direct repeat hexamers that resemble T3 response elements (T3REs); these elements are located far up-stream in the 5'-flanking DNA (Hodnett, D. W., Fantozzzi, D. A., Thurmond, D.C., Klautky, S. A., MacPhee, K. G., Estrem, S. T., Xu, G., and Goodridge, A. G. (1996) Arch. Biochem. Biophys. 334, 309-324). In transiently transfected hepatocytes, single copies of six of these elements conferred varying degrees of T3 responsiveness to linked reporter genes. In gel electrophoretic mobility shift analyses, the T3REs bound retinoid X receptor (RXR)-T3 receptor (TR) heterodimers and non- RXR/TR factors present in nuclear extracts prepared from hepatocytes. Binding of the non-RXP/TR factors was specific to individual T3REs and was unaffected by antibodies to TR or RXR. Mutagenesis of binding sites for proteins specific for T3REs 2-5 altered binding of the proteins and T3 responsiveness. These factors appear to bind to and alter function of T3REs without binding directly to TR, differentiating their actions from other TR cofactors; they were tentatively characterized as co-repressers, inhibitors, and activators of T3RE function. Together with RXR and TR, they modulate T3 responsiveness of the gene for chicken malic enzyme.

AB - Transcription of the gene for malic enzyme in chick embryo hepatocytes is stimulated about 30-fold by triiodothyronine (T3). T3 responsiveness is mediated by seven direct repeat hexamers that resemble T3 response elements (T3REs); these elements are located far up-stream in the 5'-flanking DNA (Hodnett, D. W., Fantozzzi, D. A., Thurmond, D.C., Klautky, S. A., MacPhee, K. G., Estrem, S. T., Xu, G., and Goodridge, A. G. (1996) Arch. Biochem. Biophys. 334, 309-324). In transiently transfected hepatocytes, single copies of six of these elements conferred varying degrees of T3 responsiveness to linked reporter genes. In gel electrophoretic mobility shift analyses, the T3REs bound retinoid X receptor (RXR)-T3 receptor (TR) heterodimers and non- RXR/TR factors present in nuclear extracts prepared from hepatocytes. Binding of the non-RXP/TR factors was specific to individual T3REs and was unaffected by antibodies to TR or RXR. Mutagenesis of binding sites for proteins specific for T3REs 2-5 altered binding of the proteins and T3 responsiveness. These factors appear to bind to and alter function of T3REs without binding directly to TR, differentiating their actions from other TR cofactors; they were tentatively characterized as co-repressers, inhibitors, and activators of T3RE function. Together with RXR and TR, they modulate T3 responsiveness of the gene for chicken malic enzyme.

UR - http://www.scopus.com/inward/record.url?scp=0031916827&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031916827&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.3.1613

DO - 10.1074/jbc.273.3.1613

M3 - Article

VL - 273

SP - 1613

EP - 1622

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -