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

Kristiina Tammimies, Isabel Tapia-Páez, Joëlle Rüegg, Gustaf Rosin, Juha Kere, Jan Åke Gustafsson, Ivan Nalvarte

Research output: Contribution to journalArticle

16 Scopus citations

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 α (ERα) and α (ERα). Here, we investigate the 17β-estradiol (E2)-dependent regulation of dyslexia susceptibility 1 candidate 1 (DYX1C1) expression. We demonstrate that ERα, not ERα, 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 ERα 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.

Original languageEnglish (US)
Pages (from-to)619-629
Number of pages11
JournalMolecular Endocrinology
Volume26
Issue number4
DOIs
StatePublished - Apr 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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