ERTargetDB: an integral information resource of transcription regulation of estrogen receptor target genes

Jin, Victor X.; Sun, Hao; Pohar, Twyla T.; Liyanarachchi, Sandya; Palaniswamy, Saranyan K.; Huang, Tim Hui-Ming; Davuluri, Ramana V.

doi:10.1677/jme.1.01839

Cited by 29 publications

(30 citation statements)

References 27 publications

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“…14 In the nucleus, ERα bound and activated by oestrogen is generally considered a regulator (activator or repressor) of transcription or promoter activity via two different mechanisms. 5 First, activated ERα directly binds an ERE on a promoter 22 and regulates transcription. Second, ERα binds to a half ERE, termed aERE, and further interacts with nearby DNA boundtranscription factors including members of the nuclear factor-κB (NF-κB), Sp, serum response factor and Ap families.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic upregulation of metabotropic glutamate receptor 2 in the spinal cord attenuates oestrogen-induced visceral hypersensitivity

Cao

Bai

et al. 2014

Gut

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Objective Epigenetic mechanisms are potential targets to relieve somatic pain. However, little is known whether epigenetic regulation interferes with visceral pain. Previous studies show that estrogen facilitates visceral pain. This study aimed to determine if histone hyperacetylation in the spinal cord could attenuate estrogen facilitated visceral pain. Design The effect of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) on the magnitude of the visceromotor response (VMR) to colorectal distention was examined in ovariectomized rats with/without estrogen replacement. An additional interaction with the metabotropic glutamate receptor 2/3 (mGluR2/3) antagonist LY341495 was tested. The levels of acetylated histone and mGluR2 mRNA and protein were analyzed. The binding of acetylated H3 and estrogen receptor alpha (ERα) to the GRM2 promoter were measured by chromatin immunoprecipitation (ChIP) coupled with qPCR. Results In ovariectomized rats 17β-estradiol (E2), but not safflower oil, increased the magnitude of the VMR to colorectal distention. SAHA attenuated the E2-facilitated VMR, but had no effect in safflower oil-treated rats. Subsequent spinal administration of LY341495 reversed the antinociceptive effect of SAHA in E2 rats. In addition, SAHA increased mGluR2 mRNA and protein in the spinal dorsal horn following E2, but not vehicle, treatment. In contrast, neither E2 nor SAHA alone altered mGluR2 mRNA. SAHA increased binding of H3K9ac and ERα to the same regions of the GRM2 promoter in E2-SAHA treated animals. Conclusion Histone hyperacetylation in the spinal cord attenuates the pro-nociceptive effects of estrogen on visceral sensitivity, suggesting that epigenetic regulation may be a potential approach to relieve visceral pain.

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Section: Discussionmentioning

confidence: 99%

Epigenetic upregulation of metabotropic glutamate receptor 2 in the spinal cord attenuates oestrogen-induced visceral hypersensitivity

Cao

Bai

et al. 2014

Gut

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“…Medullary ER ␣ expression after the feminizing shift may indicate a role for ER ␣ in mediating degeneration of medullary cords. While the genomic regulatory sequences of male-specific genes involved in sex cord development are not known in the slider turtle, it is worth noting that genomic screens have identified ER binding sites (estrogen response elements (ERE) sequences) in the promoter region of Sertoli cell markers Sox9 and MIS [Frasor et al, 2003;Jin et al, 2005]. In addition, the reduction in ER ␤ medullary expression may support the idea of differential roles for ER ␣ and ER ␤ isoforms during temperature-mediated feminization.…”

Section: Discussionmentioning

confidence: 99%

Steroid Signaling System Responds Differently to Temperature and Hormone Manipulation in the Red-Eared Slider Turtle <i>(Trachemys scripta elegans)</i>, a Reptile with Temperature-Dependent Sex Determination

Ramsey

Crews²

2007

Sex Dev

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Many reptiles, including the red-eared slider turtle (Trachemys scripta elegans), exhibit temperature-dependent sex determination (TSD). Temperature determines gonadal sex during the middle of embryogenesis, or the temperature-sensitive period (TSP), when gonadal sex is labile to both temperature and hormones – particularly estrogen. The biological actions of steroid hormones are mediated by their receptors as defined here as the classic transcriptional regulation of target genes. To elucidate estrogen action during sex determination, we examined estrogen receptor α (Esr1, hereafter referred to as ERα), estrogen receptor β (Esr2, hereafter referred to as ERβ), and androgen receptor (Ar, hereafter referred to as AR) expression in slider turtle gonads before, during and after the TSP, as well as following sex reversal via temperature or steroid hormone manipulation. ERα and AR levels spike at the female-producing temperature while ovarian sex is determined, but none of the receptors exhibited sexually dimorphic localization within the gonad prior to morphological differentiation. All three receptors respond differentially to sex-reversing treatments. When shifted to female-producing temperatures, embryos maintain ERα and AR expression while ERβ is reduced. When shifted to male-producing temperatures, medullary expression of all three receptors is reduced. Feminization via estradiol (E₂) treatment at a male-producing temperature profoundly changed the expression patterns for all three receptors. ERα and ERβ redirected to the cortex in E₂-created ovaries, while AR medullary expression was transiently reduced. Although warmer incubation temperature and estrogen result in the same endpoint (ovarian development), our results indicate different steroid signaling patterns between temperature- and estrogen-induced feminization.

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“…Using the web-based program ERTargetDB [21] and additional literature review, we identified 16 genes from the two ERpositive subtypes that also exhibited estrogen-responsive gene expression. Additionally, there were 13 genes identified within these two ER-positive subtypes of breast cancer that exhibited known or candidate ERE sequences.…”

Section: Introductionmentioning

confidence: 99%

A Five-Gene Model Predicts Clinical Outcome in ER+/PR+, Early-Stage Breast Cancers Treated with Adjuvant Tamoxifen

Kerr

Wittliff

2011

HORM CANC

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Primary breast carcinomas expressing both estrogen and progesterone receptors are most likely to respond to tamoxifen therapy, especially in patients with early-stage lesions. However, certain patients exhibit clinicopathologic features suggesting good prognosis relapse within 10 years, justifying a search for biomarkers identifying patients at risk for recurrence. Nine candidate genes associated with estrogen signaling were selected from microarray studies and combined with those for conventional biomarkers (ESR1, PGR, ERBB2). Expression of this 12-gene subset was analyzed by RT-qPCR in frozen tissue specimens from 60 early-stage, estrogen receptor (ER)+/progestin receptor (PR)+ breast cancers from patients treated with adjuvant tamoxifen. A multivariate model was created by Cox regression using a training data set and applied to an independent validation set. A five-gene model was developed from the training set (n = 36) that exhibited significant correlations with both relapse-free and overall survival. Applying this model to Kaplan-Meier regression, patients were separated into low-risk (100% relapse-free at 150 months) and high-risk (60% relapse-free at 150 months) groups (P = 0.03). When this model was applied to the validation set (n = 24), similar risk stratification was achieved for both relapse-free and overall survival (P = 0.01 and 0.04, respectively). We developed a five-gene model composed of PgR, BCL2, ERBB4 JM-a, RERG, and CD34 that identified early-stage, ER+/PR+ breast cancers in patients treated with tamoxifen that relapsed, although they exhibited clinicopathologic features suggesting good prognosis. Within this multivariate model, increased expression of PgR, ERBB4 JM-a, RERG, and CD34 was associated with increased survival, while increased expression of BCL2 was associated with decreased survival.

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ERTargetDB: an integral information resource of transcription regulation of estrogen receptor target genes

Cited by 29 publications

References 27 publications

Epigenetic upregulation of metabotropic glutamate receptor 2 in the spinal cord attenuates oestrogen-induced visceral hypersensitivity

Epigenetic upregulation of metabotropic glutamate receptor 2 in the spinal cord attenuates oestrogen-induced visceral hypersensitivity

Steroid Signaling System Responds Differently to Temperature and Hormone Manipulation in the Red-Eared Slider Turtle <i>(Trachemys scripta elegans)</i>, a Reptile with Temperature-Dependent Sex Determination

A Five-Gene Model Predicts Clinical Outcome in ER+/PR+, Early-Stage Breast Cancers Treated with Adjuvant Tamoxifen

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