Two Novel RXRα Isoforms from Mouse Testis

Brocard, Jacques; Kastner, Philippe; Chambon, Pierre

doi:10.1006/bbrc.1996.1782

Cited by 39 publications

(28 citation statements)

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“…T-DMRs in the Rxra gene were localized between exons 1 and 2 (Fig. 4E), where an alternative TSS for the testis-specific transcript, which is detected in liver, is located (Brocard et al 1996). These data suggested that T-DMRs could be involved in gene regulation of transcription factors, aiding liver-specific gene expression (Fig.…”

Section: Genes Encoding Transcription Factors Responsible For Expressmentioning

confidence: 83%

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

et al. 2008

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DNA methylation constitutes an important epigenetic regulation mechanism in many eukaryotes, although the extent of DNA methylation in the regulation of gene expression in the mammalian genome is poorly understood. We developed D-REAM, a genome-wide DNA methylation analysis method for tissue-dependent and differentially methylated region (T-DMR) profiling with restriction tag-mediated amplification in mouse tissues and cells. Using a mouse promoter tiling array covering a region from −6 to 2.5 kb (∼30,000 transcription start sites), we found that over 3000 T-DMRs are hypomethylated in liver compared to cerebrum. The DNA methylation profile of liver was distinct from that of kidney and spleen. This hypomethylation profile marked genes that are specifically expressed in liver, including key transcription factors such as Hnf1a and Hnf4a. Genes with T-DMRs, especially those lacking CpG islands and those with HNF-1A binding motifis in their promoters, showed good correlation between their tissue-specific expression and liver hypomethylation status. T-DMRs located downstream from their transcription start sites also showed tissue-specific gene expression. These data indicate that multilayered regulation of tissue-specific gene function could be elucidated by DNA methylation tissue profiling.

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Section: Genes Encoding Transcription Factors Responsible For Expressmentioning

confidence: 83%

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

et al. 2008

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“…1 and Ref. 8), while the location of the others remains to be identified. This is in contrast to the case of RAR␣1, for which no phosphorylation in the isoform-specific A1 region has been found (26).…”

Section: Overexpression Of Activated Jnks Increases the Phosphorylatimentioning

confidence: 94%

“…RARs are activated by both all-trans-retinoic acid (tRA) and 9-cisretinoic acid (9cRA), whereas RXRs are activated exclusively by 9cRA. There are three RAR isotypes and three RXR isotypes (␣, ␤, and ␥), encoded by distinct genes, and for each isotype, there are at least two main isoforms, which differ in their NH 2 -terminal A regions and are generated by differential promoter usage and/or alternative splicing (5,6,8). Several lines of evidence support the conclusion that RAR/RXR heterodimers are the functional units transducing the retinoid signal in vivo (Refs.…”

mentioning

confidence: 95%

Hyperphosphorylation of the Retinoid X Receptor α by Activated c-Jun NH2-terminal Kinases

Adam-Stitah¹,

Penna

Chambon

et al. 1999

Journal of Biological Chemistry

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The nuclear receptor mouse retinoid X receptor ␣ (mRXR␣) was shown to be constitutively phosphorylated in its NH 2 -terminal A/B region, which contains potential phosphorylation sites for proline-directed Ser/ Thr kinases. Mutants for each putative site were generated and overexpressed in transfected COS-1 cells. Constitutively phosphorylated residues identified by tryptic phosphopeptide mapping included serine 22 located in the A1 region that is specific to the RXR␣1 isoform. Overexpression and UV activation of the stressactivated kinases, c-Jun NH 2 -terminal kinases 1 and 2 (JNK1 and JNK2), hyperphosphorylated RXR␣, resulting in a marked decrease in its electrophoretic mobility. This inducible hyperphosphorylation involved three residues (serines 61 and 75 and threonine 87) in the B region of RXR␣ and one residue (serine 265) in the ligand binding domain (E region). Binding assays performed in vitro with purified recombinant proteins demonstrated that JNKs did not interact with RXR␣ but bound to its heterodimeric partners, retinoic acid receptors ␣ and ␥ (RAR␣ and RAR␥). Hyperphosphorylation by JNKs did not affect the transactivation properties of either RXR␣ homodimers or RXR␣/RAR␣ heterodimers in transfected cultured cells.Retinoids are derivatives of vitamin A that play key roles in a variety of biological processes ranging from pattern formation and organogenesis during embryogenesis to maintenance of homeostasis in the adult (1-4). Retinoids exert their pleiotropic effects through two classes of nuclear receptors acting as liganddependent transcriptional regulators, the retinoic acid receptors (RARs) 1 and the retinoid X receptors (RXRs) (4 -7). RARs are activated by both all-trans-retinoic acid (tRA) and 9-cisretinoic acid (9cRA), whereas RXRs are activated exclusively by 9cRA. There are three RAR isotypes and three RXR isotypes (␣, ␤, and ␥), encoded by distinct genes, and for each isotype, there are at least two main isoforms, which differ in their NH 2 -terminal A regions and are generated by differential promoter usage and/or alternative splicing (5,6,8). Several lines of evidence support the conclusion that RAR/RXR heterodimers are the functional units transducing the retinoid signal in vivo (Refs. 4 -6, 9, and 10 and references therein). However, RXRs are also able to heterodimerize with other members of the nuclear receptor superfamily, such as the thyroid hormone receptors, the vitamin D 3 receptor, and the peroxisome proliferator activated receptors (11-15).As other members of the nuclear steroid/thyroid hormone receptor superfamily, RARs and RXRs exhibit a conserved modular structure with six variably conserved functional regions (A to F) ( Fig. 1 and Refs. 5 and 6). The amino-terminal A/B region of RARs and RXRs contains a ligand-independent transactivation function AF-1 (16, 17), while the highly conserved C region is included in the DNA-binding domain. The E region is more complex, since, in addition to the ligand-binding domain, it contains a dimerization surface and a ligand-dependent tra...

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“…As no mutation was detected in the DNA of the construct used to produce the transgenic mice, the reason for this failure to correctly initiate translation remains unclear but could reflect complex interactions between 5′-untranslated MyHCα gene sequences and 5′ RXRα sequences. Despite the production of an NH 2 -terminally truncated protein, the results described here are nevertheless most probably pertinent for the role of RXRα in heart development for 2 reasons: (i) an NH 2 -terminally truncated RXRα retains most of its functional properties (DNA binding, ligand binding, and dimerization) and appears to be only minimally affected in its transactivation properties, as judged from transient transfection assays (18); and, importantly, (ii) deletion, in the mouse, of the sequences encoding the entire RXRα NH 2 -terminal region preceding the DNA binding domain does not lead to abnormal cardiac development (B. Mascrez, M. Mark, P. Kastner, and P. Chambon, unpublished study), indicating that this region is dispensable for the function of RXRα that specifies normal heart development.…”

Section: Methodsmentioning

confidence: 99%

RXRα overexpression in cardiomyocytes causes dilated cardiomyopathy but fails to rescue myocardial hypoplasia in RXRα-null fetuses

Subbarayan¹,

Mark²,

Messadeq³

et al. 2000

J. Clin. Invest.

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Two Novel RXRα Isoforms from Mouse Testis

Cited by 39 publications

References 0 publications

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

Hyperphosphorylation of the Retinoid X Receptor α by Activated c-Jun NH2-terminal Kinases

RXRα overexpression in cardiomyocytes causes dilated cardiomyopathy but fails to rescue myocardial hypoplasia in RXRα-null fetuses

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