Dataset Information

The rs3743205 SNP is important for the regulation of the dyslexia candidate gene DYX1C1 by estrogen receptor ? and DNA methylation.

ABSTRACT: Estrogen is involved in numerous physiological processes such as growth, differentiation, and function of the male and female reproductive tissues. In the developing brain, estrogen signaling has been linked to cognitive functions, such as learning and memory; however, the molecular mechanisms underlying this phenomenon are poorly understood. We have previously shown a link between developmental dyslexia and estrogen signaling, when we studied the functional interactions between the dyslexia candidate protein DYX1C1 and the estrogen receptors ? (ER?) and ? (ER?). Here, we investigate the 17?-estradiol (E2)-dependent regulation of dyslexia susceptibility 1 candidate 1 (DYX1C1) expression. We demonstrate that ER?, not ER?, binds to a transcriptionally active cis-regulatory region upstream of DYX1C1 transcriptional start site and that DYX1C1 expression is enhanced by E2 in a neuroblastoma cell line. This regulation is dependent on transcription factor II-I and liganded ER? recruitment to this region. In addition, we describe that a single nucleotide polymorphism previously shown to be associated with dyslexia and located in the cis-regulatory region of DYX1C1 may alter the epigenetic and endocrine regulation of this gene. Our data provide important molecular insights into the relationship between developmental dyslexia susceptibility and estrogen signaling.

SUBMITTER: Tammimies K

PROVIDER: S-EPMC5417142 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The rs3743205 SNP is important for the regulation of the dyslexia candidate gene DYX1C1 by estrogen receptor β and DNA methylation.

Tammimies Kristiina K Tapia-Páez Isabel I Rüegg Joëlle J Rosin Gustaf G Kere Juha J Gustafsson Jan-Åke JÅ Nalvarte Ivan I

Molecular endocrinology (Baltimore, Md.) 20120301 4

Estrogen is involved in numerous physiological processes such as growth, differentiation, and function of the male and female reproductive tissues. In the developing brain, estrogen signaling has been linked to cognitive functions, such as learning and memory; however, the molecular mechanisms underlying this phenomenon are poorly understood. We have previously shown a link between developmental dyslexia and estrogen signaling, when we studied the functional interactions between the dyslexia can ...[more]

PMID: 22383464

Similar Datasets

Project description:Estrogen receptor (ER)-beta is thought to exert anti-proliferative effects in the normal prostate but supports prostate cancer (PCa) cell survival. We previously reported that the receptor's expression declined as PCa developed in the gland but reappeared in lymph node and bone metastases. To investigate whether hypermethylation was the underlying mechanism for these phenomena, we first identified two CpG islands (CGIs) encompassing 41 CpG dinucleotides, located separately in the untranslated exon 0N and the promoter region of ER-beta. Using immunostained, laser capture-microdissected samples from 56 clinical specimens, we demonstrated an inverse relationship exists between the extent of ER-beta CGI methylation and receptor expression in normal, hyperplastic, premalignant, and malignant foci of the prostate and in lymph node and bone metastases. Treatment of PCa cell lines (LNCaP and DU145), that express little ER-beta mRNA, with a demethylating agent increased levels of receptor expression thus corroborating our in vivo findings that methylation is involved in ER-beta silencing. Methylation centers in the promoter region and exon 0N were identified by hierarchical cluster analysis of bisulfite sequencing data obtained from 710 alleles. Methylation at these centers was insignificant in normal epithelium, reached 80 to 90% in grade 4/5 PCa, but declined to less than 20% in bone metastases. In addition, progressive methylation spreading from the exonic CGI to the promoter CGI, which correlated with loss of ER-beta expression, was detected in microdissected samples and in cell cultures. Using a new class of methylated oligonucleotides that mediate sequence-specific methylation in cellulo, we demonstrated that methylation of the promoter CGI, but not the exonic CGIs, led to transcriptional inactivation of ER-beta. Our results present the first evidence that epigenetic regulation of ER-beta is a reversible and tumor stage-specific process and that gene silencing via methylated oligonucleotides may have therapeutic potential in the treatment of advanced PCa.

Dataset Information

The rs3743205 SNP is important for the regulation of the dyslexia candidate gene DYX1C1 by estrogen receptor ? and DNA methylation.

Publications

The rs3743205 SNP is important for the regulation of the dyslexia candidate gene DYX1C1 by estrogen receptor β and DNA methylation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets