The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Cary N. Mariash - One of the best experts on this subject based on the ideXlab platform.
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human spot 14 glucose and thyroid Hormone Response characterization and thyroid Hormone Response Element identification
Endocrinology, 2003Co-Authors: Mark C. Campbell, Grant W. Anderson, Cary N. MariashAbstract:Spot 14 is a 17-kDa protein expressed in lipogenic tissues and is postulated to play a role in thyroid Hormone stimulation of lipogenesis. To further our understanding of Spot 14 regulation in humans, our laboratory recently cloned the human Spot 14 gene. The gene is highly homologous to the rat Spot 14 ortholog and located on a chromosomal region implicated in human obesity. Because our understanding of Spot 14 transcriptional regulation is derived from rat promoter studies, we assessed the thyroid Hormone responsivity of the human Spot 14 promoter. These studies revealed a significantly greater thyroid Hormone Response for the human promoter, compared with the rat. Deletional studies of the human Spot 14 promoter reveal a 774-bp region at approximately position −2700, which is both necessary and sufficient for the thyroid Hormone Response. EMSAs with subfragments from this region identify a 146-bp DNA fragment capable of binding a TRβ1-retinoid X receptor heterodimer. Site-directed mutagenesis confirmed...
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Human spot 14 glucose and thyroid Hormone Response: characterization and thyroid Hormone Response Element identification.
Endocrinology, 2003Co-Authors: Mark C. Campbell, Grant W. Anderson, Cary N. MariashAbstract:Spot 14 is a 17-kDa protein expressed in lipogenic tissues and is postulated to play a role in thyroid Hormone stimulation of lipogenesis. To further our understanding of Spot 14 regulation in humans, our laboratory recently cloned the human Spot 14 gene. The gene is highly homologous to the rat Spot 14 ortholog and located on a chromosomal region implicated in human obesity. Because our understanding of Spot 14 transcriptional regulation is derived from rat promoter studies, we assessed the thyroid Hormone responsivity of the human Spot 14 promoter. These studies revealed a significantly greater thyroid Hormone Response for the human promoter, compared with the rat. Deletional studies of the human Spot 14 promoter reveal a 774-bp region at approximately position -2700, which is both necessary and sufficient for the thyroid Hormone Response. EMSAs with subfragments from this region identify a 146-bp DNA fragment capable of binding a TRbeta1-retinoid X receptor heterodimer. Site-directed mutagenesis confirmed the identity of a candidate DR-4 thyroid Hormone Response Element within this fragment that is similar, but not identical, to the two rat Spot 14 thyroid Hormone Response Elements. We hypothesize that the difference in thyroid Hormone Response between the orthologous promoters may allow a selective advantage to each species based on their different nutritional and physiological niches.
Mark C. Campbell - One of the best experts on this subject based on the ideXlab platform.
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human spot 14 glucose and thyroid Hormone Response characterization and thyroid Hormone Response Element identification
Endocrinology, 2003Co-Authors: Mark C. Campbell, Grant W. Anderson, Cary N. MariashAbstract:Spot 14 is a 17-kDa protein expressed in lipogenic tissues and is postulated to play a role in thyroid Hormone stimulation of lipogenesis. To further our understanding of Spot 14 regulation in humans, our laboratory recently cloned the human Spot 14 gene. The gene is highly homologous to the rat Spot 14 ortholog and located on a chromosomal region implicated in human obesity. Because our understanding of Spot 14 transcriptional regulation is derived from rat promoter studies, we assessed the thyroid Hormone responsivity of the human Spot 14 promoter. These studies revealed a significantly greater thyroid Hormone Response for the human promoter, compared with the rat. Deletional studies of the human Spot 14 promoter reveal a 774-bp region at approximately position −2700, which is both necessary and sufficient for the thyroid Hormone Response. EMSAs with subfragments from this region identify a 146-bp DNA fragment capable of binding a TRβ1-retinoid X receptor heterodimer. Site-directed mutagenesis confirmed...
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Human spot 14 glucose and thyroid Hormone Response: characterization and thyroid Hormone Response Element identification.
Endocrinology, 2003Co-Authors: Mark C. Campbell, Grant W. Anderson, Cary N. MariashAbstract:Spot 14 is a 17-kDa protein expressed in lipogenic tissues and is postulated to play a role in thyroid Hormone stimulation of lipogenesis. To further our understanding of Spot 14 regulation in humans, our laboratory recently cloned the human Spot 14 gene. The gene is highly homologous to the rat Spot 14 ortholog and located on a chromosomal region implicated in human obesity. Because our understanding of Spot 14 transcriptional regulation is derived from rat promoter studies, we assessed the thyroid Hormone responsivity of the human Spot 14 promoter. These studies revealed a significantly greater thyroid Hormone Response for the human promoter, compared with the rat. Deletional studies of the human Spot 14 promoter reveal a 774-bp region at approximately position -2700, which is both necessary and sufficient for the thyroid Hormone Response. EMSAs with subfragments from this region identify a 146-bp DNA fragment capable of binding a TRbeta1-retinoid X receptor heterodimer. Site-directed mutagenesis confirmed the identity of a candidate DR-4 thyroid Hormone Response Element within this fragment that is similar, but not identical, to the two rat Spot 14 thyroid Hormone Response Elements. We hypothesize that the difference in thyroid Hormone Response between the orthologous promoters may allow a selective advantage to each species based on their different nutritional and physiological niches.
Herbert H. Samuels - One of the best experts on this subject based on the ideXlab platform.
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The herpes simplex virus thymidine kinase gene promoter contains a novel thyroid Hormone Response Element.
Molecular endocrinology (Baltimore Md.), 1993Co-Authors: Hae-young Park, D. Davidson, Bruce M. Raaka, Herbert H. SamuelsAbstract:Thyroid Hormone (T3) receptors (T3Rs) regulate transcription by binding to T3 Response Elements (TREs) located within promoter regions of T3-regulated genes. In rat pituitary GH4C1 cells, expression of a reporter containing herpes simplex virus thymidine kinase (TK) gene sequences (-105/+51) linked to the chloramphenicol acetyltransferase gene was stimulated 4- to 5-fold by T3. Linker scanning mutants of the TK promoter revealed that regions around -80 containing a CTF/NF-1 recognition sequence and around -10 are both required for regulation by T3. Endogenous T3Rs from GH4C1 cells labeled with [125I]T3 bound only to TK promoter DNA fragments containing the -10 region. The -22/-2 sequence (TK-TRE) contains half-sites oriented as an inverted repeat separated by 6 basepairs that are identical to and similar to an optimized TRE half-site. Purified chicken T3R alpha 1 forms apparent monomeric and dimeric complexes on the 32P-labeled TK-TRE, as found previously with an inverted repeat of the optimized TRE (TREp) with no basepair gap. T3 enhances the formation and alters the mobility of these complexes on both Elements. When positioned up-stream of a heterologous promoter-chloramphenicol acetyltransferase reporter, the TK-TRE conferred T3 regulation by endogenous T3R in GH4C1 cells and by cotransfected chicken T3R alpha 1 in HeLa cells. The TK-TRE does not bind and is not activated by retinoic acid receptor. T3Rs and nuclear proteins from GH4C1, HeLa, and COS1 cells form heterodimers on the TK-TRE which differ in abundance and mobility from heterodimers formed on the TREp. The identification of a TRE in the TK promoter raises the possibility that T3R or related proteins may play important roles in regulating the life cycle of herpes simplex virus.
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the herpes simplex virus thymidine kinase gene promoter contains a novel thyroid Hormone Response Element
Molecular Endocrinology, 1993Co-Authors: Hae-young Park, D. Davidson, Bruce M. Raaka, Herbert H. SamuelsAbstract:Thyroid Hormone (T3) receptors (T3Rs) regulate transcription by binding to T3 Response Elements (TREs) located within promoter regions of T3-regulated genes. In rat pituitary GH4C1 cells, expression of a reporter containing herpes simplex virus thymidine kinase (TK) gene sequences (-105/+51) linked to the chloramphenicol acetyltransferase gene was stimulated 4- to 5-fold by T3. Linker scanning mutants of the TK promoter revealed that regions around -80 containing a CTF/NF-1 recognition sequence and around -10 are both required for regulation by T3. Endogenous T3Rs from GH4C1 cells labeled with [125I]T3 bound only to TK promoter DNA fragments containing the -10 region. The -22/-2 sequence (TK-TRE) contains half-sites oriented as an inverted repeat separated by 6 basepairs that are identical to and similar to an optimized TRE half-site. Purified chicken T3R alpha 1 forms apparent monomeric and dimeric complexes on the 32P-labeled TK-TRE, as found previously with an inverted repeat of the optimized TRE (TREp...
Barry G. W. Arnason - One of the best experts on this subject based on the ideXlab platform.
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β-Trace Gene Expression Is Regulated by a Core Promoter and a Distal Thyroid Hormone Response Element
The Journal of biological chemistry, 1997Co-Authors: David M. White, Teiji Takeda, Leslie J. Degroot, Kari Stefansson, Barry G. W. ArnasonAbstract:We isolated and characterized the human beta-Trace protein (betaTP) gene promoter. betaTP, also known as prostaglandin D2 synthase, is a lipocalin secreted from the choroid plexus and meninges into cerebrospinal fluid. Basal transcription of the betaTP gene is directed from a core promoter found within the first 325 bases of the 5'-flanking sequence. The betaTP gene promoter is responsive to thyroid Hormone (3,3',5-triiodothyronine, T3) and efficiently repressed by unliganded human thyroid Hormone receptor beta (TRbeta). Functional analysis of the betaTP promoter in TE671 cells revealed that responsiveness to T3 occurs in sequences 2.5 kilobase pairs 5' of the start site. Within the Hormone-responsive region we identified a thyroid Hormone Response Element (TRE) located from -2576 to -2562 base pairs relative to the transcription start site. The betaTP TRE is composed of two directly repeated consensus half-sites separated by a 3-base pair space (DR3). The betaTP TRE forms specific complexes with TRbeta. We have shown that a gene active in the choroid plexus and meninges is responsive to T3. T3 may play a role in the regulated transport of substances into the cerebrospinal fluid and ultimately the brain.
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β trace gene expression is regulated by a core promoter and a distal thyroid Hormone Response Element
Journal of Biological Chemistry, 1997Co-Authors: David M. White, Teiji Takeda, Leslie J. Degroot, Kari Stefansson, Barry G. W. ArnasonAbstract:Abstract We isolated and characterized the human β-Trace protein (βTP) gene promoter. βTP, also known as prostaglandin D2 synthase, is a lipocalin secreted from the choroid plexus and meninges into cerebrospinal fluid. Basal transcription of the βTP gene is directed from a core promoter found within the first 325 bases of the 5′-flanking sequence. The βTP gene promoter is responsive to thyroid Hormone (3,3′,5-triiodothyronine, T3) and efficiently repressed by unliganded human thyroid Hormone receptor β (TRβ). Functional analysis of the βTP promoter in TE671 cells revealed that responsiveness to T3 occurs in sequences 2.5 kilobase pairs 5′ of the start site. Within the Hormone-responsive region we identified a thyroid Hormone Response Element (TRE) located from −2576 to −2562 base pairs relative to the transcription start site. The βTP TRE is composed of two directly repeated consensus half-sites separated by a 3-base pair space (DR3). The βTP TRE forms specific complexes with TRβ. We have shown that a gene active in the choroid plexus and meninges is responsive to T3. T3 may play a role in the regulated transport of substances into the cerebrospinal fluid and ultimately the brain.
Béatrice Desvergne - One of the best experts on this subject based on the ideXlab platform.
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Feedback on hypothalamic TRH transcription is dependent on thyroid Hormone receptor N terminus.
Molecular endocrinology (Baltimore Md.), 2002Co-Authors: Hajer Guissouma, Béatrice Desvergne, Sandrine M. Dupre, Nathalie Becker, Elisabeth Jeannin, Isabelle Seugnet, Barbara A. DemeneixAbstract:The beta thyroid Hormone receptor (TRbeta), but not TRalpha1, plays a specific role in mediating T(3)-dependent repression of hypothalamic TRH transcription. To investigate the structural basis of isoform specificity, we compared the transcriptional regulation and DNA binding obtained with chimeric and N-terminally deleted TRs. Using in vivo transfection assays to follow hypothalamic TRH transcription in the mouse brain, we found that TRbeta1 and chimeras with the TRbeta1 N terminus did not affect either transcriptional activation or repression from the rat TRH promoter, whereas N-terminally deleted TRbeta1 impaired T(3)-dependent repression. TRalpha1 or chimeras with the TRalpha1 N terminus reduced T(3)-independent transcriptional activation and blocked T(3)-dependent repression of transcription. Full deletion of the TRalpha1 N terminus restored ligand-independent activation of transcription. No TR isoform specificity was seen after transcription from a positive thyroid Hormone Response Element. Gel mobility assays showed that all TRs tested bound specifically to the main negative thyroid Hormone Response Element in the TRH promoter (site 4). Addition of neither steroid receptor coactivator 1 nor nuclear extracts from the hypothalamic paraventricular nuclei revealed any TR isoform specificity in binding to site 4. Thus N-terminal sequences specify TR T(3)-dependent repression of TRH transcription but not DNA recognition, emphasizing as yet unknown neuron-specific contributions to protein-promoter interactions in vivo.
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The major transcription initiation site of the SV40 late promoter is a potent thyroid Hormone Response Element
Nucleic acids research, 1997Co-Authors: Béatrice Desvergne, Tatiana FavezAbstract:Thyroid Hormone receptors (TRs) are members of the nuclear Hormone receptor superfamily, which act as transcription factors upon binding to specific DNA sequences called thyroid Hormone (T3) Response Elements (TREs). Such Elements are found in the upstream regulatory region of promoters as well as in intragenic sequences of T3-responsive genes. In this report, we demonstrate that SV40 late (SVL) promoter activity is strongly down-regulated by TR in the absence of ligand. Addition of T3 releases this repression, but does not further induce SVL promoter activity. Electrophoretic mobility shift analyses reveal a TR binding Element that overlaps with the SV40 major late transcription initiation site. This Element closely fits the consensus TRE, formed of two hexanucleotides organized in a tandem repeat separated by 4 nt, and is able to confer T3 responsiveness on a heterologous promoter. We further show that, although the presence of TR leads to quantitatively modified expression of an SVL-driven reporter gene, neither displacement of the site of transcription initiation nor modification of the splicing pattern of the primary transcripts occur.
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Characterization of myelin basic protein thyroid Hormone Response Element and its function in the context of native and heterologous promoter.
The Journal of biological chemistry, 1992Co-Authors: Antonella Farsetti, Béatrice Desvergne, P Hallenbeck, Jacob Robbins, Vera M. NikodemAbstract:Abstract In this report we have characterized further the myelin basic protein (MBP) gene thyroid Hormone Response Element (TRE) by functional and binding analysis. Mutation and deletion experiments revealed that this TRE, confined to the sequences -184 to -167 of the MBP promoter, is able to function as a classical regulatory Element in the context of the native and a heterologous promoter. It is comprised of two regions, containing a motif that is highly conserved among other TREs: AGGACA, arranged as an inverted palindrome. Any mutation within the footprinted region impaired receptor binding and function. Moreover, the deletion of sequences outside of the receptor footprinted region (MBP-TRE-18) resulted in a higher triiodothyronine responsiveness and a concomitant increase in receptor-dependent, Hormone-independent repression. Results of transfection assays showed that both receptors alpha and beta elicit indistinguishable triiodothyronine Responses when the MBP-TRE functions as a regulator of a heterologous promoter activity. However, a preferential beta receptor transactivation was observed when the MBP-TRE was placed in the context of its native promoter.
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Functional characterization and receptor binding studies of the malic enzyme thyroid Hormone Response Element.
The Journal of biological chemistry, 1991Co-Authors: Béatrice Desvergne, K J Petty, Vera M. NikodemAbstract:We previously showed that the 5'-flanking region of the malic enzyme (ME) gene contains a cis-regulatory Element (-281 to -261) that binds thyroid Hormone receptors and confers triiodothyronine (T3) inducibility of transcription to the ME promoter (Petty, K.J., Desvergne, B., Mitsuhashi, T., and Nikodem, V. M. (1990) J. Biol. Chem. 265, 7395-7400). In this report, we have used deletion and mutation analyses of the ME thyroid Hormone Response Element (TRE) to evaluate the roles of several subregions of TRE in T3 binding and transactivation. ME TRE was shown to act as an enhancer conferring T3 responsiveness to a heterologous promoter thymidine kinase. Although T3 treatment induced the promoter activity, the absence of Hormone resulted in repression as measured by the level of chloramphenicol acetyltransferase expression in the NIH 3T3 transient expression system in the presence of overexpressed receptor. The degree of repression was similar to the degree of T3 induction observed for the same TRE mutants. Mutation and deletion analyses indicated that the functional TRE is comprised of discrete regions that are not contiguous, with a dominant role of a cluster of G residues and an AGGACA sequence. Both functions, induction and repression of transcription, correlated with receptor binding to the ME TRE as determined by competition binding assays using wild type and mutated TRE as competitors.