The untranslated first exon ‘exon OS’ of the rat estrogen receptor (ER) gene

Hirata, Shuji; Koh, Tomoko; Yamada-Mouri, Naoko; Hoshi, Kazuhiko; Kato, Junzo

doi:10.1016/0014-5793(96)00987-8

Cited by 27 publications

(21 citation statements)

References 14 publications

(27 reference statements)

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“…These regions act as molecular switches that activate or deactivate transcription initiation through differential methylation mechanisms (Sasaki et al 2003, Champagne et al 2006. In the rat, it has been described that a system of untranslated first exons is associated with the promoter selection for ERa transcription initiation, and to date five active promoters called OS, ON, O, OT, and E1 (Koike et al 1987, Hirata et al 1996a,b, Donaghue et al 1999, Osada et al 2001) have been identified. Little is known about the precise function of each ERa promoter; however, it has been reported that a mechanism of promoter selection is involved in the complex stage-and region-specific regulation of ERa gene expression in many organs, including the rat brain (Kato et al 1998, Hamada et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

Monje¹,

Varayoud²,

Luque³

et al. 2007

Journal of Endocrinology

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The xenoestrogen bisphenol A (BPA) is commonly ingested by humans. We examined the effects of neonatal exposure to low versus high doses of BPA over the control of estrogen receptor a (ERa) expression in the preoptic area (POA) of prepubertal female rats. Pups received s.c. injections every 48 h of BPA (high dose, 20 mg/kg and low dose, 0 . 05 mg/kg) or diethylstilbestrol (DES, 0 . 02 mg/kg) from postnatal day (PND) 1 to PND7 and were killed at PND8 or PND21. Relative expression of ERa transcripts containing alternative 5 0 -untranslated regions OS, ON, O, OT, and E1 in POA were evaluated by RT-PCR. Methylation status of ERa promoters was determined by bisulfited DNA restriction analysis and ERa protein by immunohistochemistry. In PND8, the high dose of BPA and DES diminished total ERa mRNA levels, mediated by the decreased expression of ERa-O and ERa-OT variants. In contrast, the low dose of BPA augmented total ERa mRNA by increasing the expression of the ERa-E1 variant. In PND21, both BPA doses increased total ERa mRNA by means of the augmented expression of ERa-O and ERa-OT variants. In PND21, the methylation status of the ERa promoters and the circulating levels of estradiol were similar in all experimental groups. At PND8 and PND21, DES and the high dose of BPA decreased, while the low dose of BPA increased ERa protein in the POA. These findings show that neonatal BPA exposure alters the abundance of hypothalamic ERa transcript variants and protein in a dose-dependent manner.

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Section: Introductionmentioning

confidence: 99%

Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

Monje¹,

Varayoud²,

Luque³

et al. 2007

Journal of Endocrinology

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“…A system of untranslated exons and regulatory elements determine ERα transcription initiation [56,57,58]. Estrogens are known to regulate the selective usage of these promoter systems [59] and although it has not been explicitly tested, sex differences in ERα promoter methylation may be related to alternative promoter selection and thereby involved in sexual differentiation of the brain.…”

Section: Sex-specific Dna Methylation During Development and Beyondmentioning

confidence: 99%

Epigenetic Underpinnings of Developmental Sex Differences in the Brain

2011

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Sexual differentiation of the brain is a crucial developmental process that enables the lifelong expression of sexually dimorphic behaviors, including those necessary for successful reproduction. During a perinatal sensitive period, gonadal hormones defeminize and masculinize the male brain, and a lack of gonadal steroids allows for feminization in the female. This hormonally-induced differentiation permanently alters neural structures, creating highly dimorphic brain regions; however, the mechanism by which hormones exert their long-lasting effects are still largely unknown. Epigenetic processes such as DNA methylation and histone modifications serve as an interface for environmental stimuli to exert control over the genome. These modifications have the capacity to activate or repress gene expression, thereby shaping the developmental outcomes of cells, circuits, and structures in the brain. Sex differences in methylation, methyl-binding proteins, and chromatin modifications indicate that epigenetic mechanism may be important for sexual differentiation of the brain. The data outlined in this review provide evidence that gonadal hormones in the neonatal brain influence epigenetic processes such as DNA methylation and histone acetylation, but also emphasize the primitive status of our current understanding of epigenetics and sexual differentiation and the brain.

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“…Six hER␣ messenger RNA (mRNA) isoforms (A-F hER␣ mRNAs) are generated by the alternative splicing of five upstream exons (1B-1F) to a common site upstream of the translation start codon (12a). Similarly, at least three ER␣ mRNA forms have been identified in the rat (13)(14)(15). These data suggest that alternative 5Ј-splicing and promoter usage is probably a general feature of the ER␣ genes in mammals.…”

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confidence: 71%

Identification of Novel Chicken Estrogen Receptor-α Messenger Ribonucleic Acid Isoforms Generated by Alternative Splicing and Promoter Usage**This work was supported by the Irish American Partnership (to C.G.), the Irish Cancer Society, and an EMBO long term fellowship (to G.F.).

et al. 1998

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Using the rapid amplification of complementary DNA ends (RACE) methodology we have identified three new chicken estrogen receptor-␣ (cER␣) messenger RNA (mRNA) variants in addition to the previously described form (isoform A). Whereas one of the new variants (isoform B) presents a 5Ј-extremity contiguous to the 5Ј-end of isoform A, the two other forms (isoforms C and D) are generated by alternative splicing of upstream exons (C and D) to a common site situated 70 nucleotides upstream of the translation start site in the previously assigned exon 1 (A). The 3Ј-end of exon 1C has been located at position Ϫ1334 upstream of the transcription start site of the A isoform (ϩ1). Whereas the genomic location of exon 1D is unknown, 700 bp 5Ј to this exon were isolated by genomic walking, and their sequence was determined. The transcription start sites of the cER␣ mRNA isoforms were defined. In transfection experiments, the regions immediately upstream of the A-D cER␣ mRNA isoforms were shown to possess cell-specific promoter activities. Three of these promoters were down-regulated in the presence of estradiol and ER␣ protein. It is concluded, therefore, that the expression of the four different cER␣ mRNA isoforms is under the control of four different promoters. Finally, RT-PCR, S1 nuclease mapping, and primer extension analysis of these different cER␣ mRNA isoforms revealed a differential pattern of expression of the cER␣ gene in chicken tissues. Together, the results suggest that alternative 5Ј-splicing and promoter usage may be mechanisms used to modulate the levels of expression of the chicken ER␣ gene in a tissue-specific and/or developmental stage-specific manner. (Endocrinology 139: 4614 -4625, 1998) T HE STEROID hormone estrogen is ubiquitous in nature; it is found in yeast, fish, reptiles, birds, and all mammals (1). In all vertebrates, its main function is in the control of reproduction. Of equal physiological importance is the fact that estrogen also orchestrates intricate pathways in bone, liver, and fat metabolism; embryogenesis; homeostasis; and the cardiovascular system (2, 3). Specific to oviparous species, one of the main target organs for estrogens is the liver, as vitellogenesis is controlled predominantly by this hormone (4, 5).Estrogen exerts its potent physiological effects by binding to its cognate receptors, the estrogen receptors (ER), intracellularly. To date, two nuclear ERs (ER␣ and ER␤), encoded by different genes in a tissue-specific manner, have been identified in mammals (6 -10). Although it is highly probable that the ER␤ form is also present and expressed in some tissues in oviparous vertebrates, its existence remains to be demonstrated in these species. The ER␣ and -␤ proteins belong to the steroid/thyroid hormone/retinoic acid receptor family whose members act as ligand-inducible transcription factors (11). Receptors of this family are characterized by a unique modular structure. Discrete functional domains (named A-F), which include regions required for DNA binding, ligand bi...

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The untranslated first exon ‘exon OS’ of the rat estrogen receptor (ER) gene

Cited by 27 publications

References 14 publications

Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

Epigenetic Underpinnings of Developmental Sex Differences in the Brain

Identification of Novel Chicken Estrogen Receptor-α Messenger Ribonucleic Acid Isoforms Generated by Alternative Splicing and Promoter Usage**This work was supported by the Irish American Partnership (to C.G.), the Irish Cancer Society, and an EMBO long term fellowship (to G.F.).

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