Identification of Functional Positive and Negative Thyroid Hormone-Responsive Elements in the Rat Apolipoprotein AI Promoter

Taylor, Anthony H.; Wishart, Paul; Lawless, DeSales; Raymond, Jacques; Wong, Norman C.W.

doi:10.1021/bi960269o

Cited by 55 publications

(47 citation statements)

References 54 publications

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“…see [14]) binds to the given core promoter. In some cases, hormone receptors may in fact bind at either the immediately proximal side of the TATA box or over the initiator site, sterically blocking transcription complexes from binding to the promoter [15][16][17][18]. The regulation of transcription of either hormone-sensitive or other genes is considered to be to a large extent determined by its character as a TATA-box-dominated or initiator-dominated promoter, since most eukaryotic genes appear to be sufficed by the presence or action of only one of these two elements.…”

Section: Introductionmentioning

confidence: 99%

Transcription of the juvenile hormone esterase gene under the control of both an initiator and AT-rich motif

Jones

Mańczak

Schelling

et al. 1998

Biochemical Journal

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The binding of transcription factors to the core promoter of the juvenile hormone esterase gene was functionally characterized using both a cell-free in vitrotranscription functional assay and a cell transfection assay. A core JHE promoter (-61 to +28 bp relative to transcription start site) supported faithful transcription from the in vivo transcription start site. The nuclear extracts from the Sf9 insect cell line that provided transcription from that template also bound to that template as a probe in gel-mobility shift assays. Deletion or transversion of the initiator-binding motif (-1 to +4 bp) abolished detectable transcription either in vitro or in transfected cells. An AT-rich motif (ATATAT; -28 to -23 bp) serves another transcription factor-binding site. Mutation of the AT-rich motif to a canonical TATA-box preserved transcription, while either its deletion or complete transversion abolished or significantly reduced detectable transcriptional activity. These results indicate that, under these conditions, the functional operation of this core promoter approaches that of a composite promoter in which both the TATA- and initiator-binding protein complexes are necessary, even for basal transcription. On the other hand, these debilitating mutations to either the TATA box or initiator motif did not prevent the ability of the corresponding gel-shift competitive probes to compete with the wild-type promoter for binding by the transcription factors. Even a double transversion of both the AT-rich motif and the initiator-binding motif was able to competitively displace the protein complex that bound to the labelled wild-type probe. These data strongly indicate the presence of (an) additional core-promoter-associated transcription factor(s) (that is not the ‘downstream element ’) that contact(s) the AT-binding complex and/or initiator-binding factor with sufficient avidity to remove them from binding to the competing wild-type promoter sequence.

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Section: Introductionmentioning

confidence: 99%

Transcription of the juvenile hormone esterase gene under the control of both an initiator and AT-rich motif

Jones

Mańczak

Schelling

et al. 1998

Biochemical Journal

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“…The complex TRE in the TSH gene contains a palindrome that activates and an independent half-site that mediates binding of a monomer of T3R and repression of transcription (11,12). Similarly the TRE in thyrotropin-releasing hormone and apolipoprotein A1 genes contains a complex element that involves the T3R monomer and a T3R-RXR heterodimer (13,14). Furthermore, formation of a monomer ϩ homodimer of GR was found to inhibit transcription of the POMC gene (15).…”

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confidence: 99%

Negative Response Elements in Keratin Genes Mediate Transcriptional Repression and the Cross-talk among Nuclear Receptors

Jho¹,

Radoja²,

Im³

et al. 2001

Journal of Biological Chemistry

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Very little is known about the mechanisms responsible for the findings that binding of nuclear receptors (NR) to some promoter elements leads to transcriptional activation, whereas binding to others leads to repression. Case in point is the group of epidermal keratin genes and their DNA sequences responsible for repression by NR. Keratin response elements (KREs) interact with receptors for retinoic acid, thyroid hormone, and glucocorticoids. KREs, by their structure and sequence, direct the binding of retinoic acid and thyroid hormone as homodimers and glucocorticoids as monomers. Such specific DNA-receptor interactions are crucial for the repression signal of transcription. In this paper we have analyzed the interactions between the KREs and NR that lead to such repression. We have found that KREs are promoter-independent. They not only provide a docking platform for the receptors, but also play a key role in directing the receptors to bind into particular configurations and coordinating the interactions among different receptors. Both an intact KRE and an intact receptor DNA-binding domain are necessary for the regulation to occur, which emphasizes the importance of interaction between the DNA and NR for proper signaling. Furthermore, KREs allow simultaneous binding of multiple receptors, thus providing fine-tuning of transcriptional regulation. The DNA/DNA-binding domain interactions in keratin promoters exemplify tissue and gene specificity of hormone action.

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“…Transcription of the apoA 1 gene is regulated by several hormones and second messengers, including retinoids (Zolfagari & Ross 1994), insulin (Murao et al 1998, Hargrove et al 1999, thyroid hormone (Mooradian et al 1996, Taylor et al 1996b, sex hormones (Patsch et al 1980, Harnish et al 1998, and others (Taylor et al 1996a, Vu-Dac et al 1998, Murao et al 1997. Several of these pathways function to increase the expression of the apoA 1 gene, whereas others act to decrease apoA 1 gene expression.…”

Section: Introductionmentioning

confidence: 99%

“…This element is also responsible for induction of the apoA 1 gene by insulin (Murao et al 1998). Likewise, thyroid hormone can act as either a transcriptional enhancer or, in a more artificial fashion, as a transcriptional repressor (Taylor et al 1996b). The enhancer effect requires the presence of a thyroid hormone response element (TRE) located between nucleotides 208 and 193, in site A (Taylor et al 1996b), whereas the repressor effect is observed only when the TRE in site A is removed from reporter constructs, and requires the presence of a negative TRE (nTRE), AGGTCA, located between nucleotides 25 and 20.…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, thyroid hormone can act as either a transcriptional enhancer or, in a more artificial fashion, as a transcriptional repressor (Taylor et al 1996b). The enhancer effect requires the presence of a thyroid hormone response element (TRE) located between nucleotides 208 and 193, in site A (Taylor et al 1996b), whereas the repressor effect is observed only when the TRE in site A is removed from reporter constructs, and requires the presence of a negative TRE (nTRE), AGGTCA, located between nucleotides 25 and 20. In this case, the nTRE, located 3 end adjacent to the apoA 1 TATA box, acts as a transcriptional repressor in the presence of the ligand-activated thyroid hormone receptor (THR) (Taylor et al 1996b, Carr & Wong 1994.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of apoA1 gene expression with acidosis: requirement for a transcriptional repressor

Haas¹,

Reinacher²,

Jp³

et al. 2001

Journal of Molecular Endocrinology

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Serum apolipoprotein A 1 (apoA 1 ) concentration is inversely correlated with the risk of premature atherosclerosis. Serum apoA 1 concentrations are regulated, in part, at the transcriptional level. ApoA 1 mRNA is synthesized primarily in the liver and small intestine, under the direction of a number of signaling molecules and tissue-specific regulatory elements. Previously, we demonstrated that extracellular acidosis suppresses apoA 1 mRNA levels at the level of transcription. Here we demonstrate that intracellular acidosis, in the absence of extracellular pH changes, represses apoA 1 promoter activity. Repression occurs through a pH responsive element (pH-RE) located within the apoA 1 gene promoter. Acidosis increases the specific DNA binding activity of a putative repressor protein within the immediate 5 -flanking region of the apoA 1 gene. The cis-element that binds the putative repressor protein contains a negative thyroid hormone response element (nTRE) located 3 and adjacent to the apoA 1 TATA box. Mutation of the nTRE/ pH-RE abrogates protein binding and alters the activity of reporter genes controlled by this element. Repression by acidosis did not require de novo mRNA and protein synthesis. Inhibition of tyrosine kinase activity and diacylglycerol-stimulated protein kinase C (PKC) signaling pathways with tyrophostin A47 and phorbol myristate acetate, respectively, did not affect the repression of apoA 1 promoter activity with acidosis. These results suggest that transcriptional repression of the apoA 1 gene by alterations in ambient pH is associated with enhanced DNA binding activity of a repressor protein, through a mechanism which appears to be independent of de novo mRNA and protein synthesis, tyrosine kinase activity, or PKC activation.

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Identification of Functional Positive and Negative Thyroid Hormone-Responsive Elements in the Rat Apolipoprotein AI Promoter

Cited by 55 publications

References 54 publications

Transcription of the juvenile hormone esterase gene under the control of both an initiator and AT-rich motif

Transcription of the juvenile hormone esterase gene under the control of both an initiator and AT-rich motif

Negative Response Elements in Keratin Genes Mediate Transcriptional Repression and the Cross-talk among Nuclear Receptors

Regulation of apoA1 gene expression with acidosis: requirement for a transcriptional repressor

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