Open AccessThe rs3743205 SNP Is Important for the Regulation of the Dyslexia Candidate GeneDYX1C1by Estrogen Receptor β and DNA Methylation
Author(s) -
Kristiina Tammimies,
Isabel Tapia-Páez,
Joëlle Rüegg,
Gustaf Rosin,
Juha Kere,
Jan Åke Gustafsson,
Ivan Nalvarte
Publication year - 2012
Publication title -
molecular endocrinology
Language(s) - English
Resource type - Journals
eISSN - 1944-9917
pISSN - 0888-8809
DOI - 10.1210/me.2011-1376
Subject(s) - biology , dna methylation , dyslexia , epigenetics , estrogen receptor , estrogen receptor alpha , genetics , transcription factor , estrogen receptor beta , regulation of gene expression , candidate gene , gene , microbiology and biotechnology , gene expression , reading (process) , cancer , breast cancer , political science , law
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 β (ERβ). Here, we investigate the 17β-estradiol (E2)-dependent regulation of dyslexia susceptibility 1 candidate 1 (DYX1C1) expression. We demonstrate that ERβ, 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 ERβ 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.