Abstract
Gonadal hormone 17β-estradiol (E2) and its receptors are key regulators of gene transcription by binding to estrogen responsive elements in the genome. Besides the classical genomic action, E2 regulates gene transcription via the modification of epigenetic marks on DNA and histone proteins. Depending on the reaction partner, liganded estrogen receptor (ER) promotes DNA methylation at the promoter or enhancer regions. In addition, ERs are important regulators of passive and active DNA demethylation. Furthermore, ERs cooperating with different histone modifying enzymes and chromatin remodeling complexes alter gene transcription. In this review, we survey the basic mechanisms and interactions between estrogen receptors and DNA methylation, demethylation and histone modification processes as well as chromatin remodeling complexes. The particular relevance of these mechanisms to physiological processes in memory formation, embryonic development, spermatogenesis and aging as well as in pathophysiological changes in carcinogenesis is also discussed.
Highlights
Epigenetics can be defined as “heritable changes in genome function that occur without changes in the DNA sequence” [1,2]
In order to understand the mechanism of E2-induced methylation, we first discuss the role of CpG islands
Since DNMT3b is a de novo methyl transferase, these results suggest that ERα has a role in the formation of new DNA methylation and alters the initiation of transcription via DNA methyltransferases (DNMTs)-mediated DNA methylation [33]
Summary
Epigenetics can be defined as “heritable changes in genome function that occur without changes in the DNA sequence” [1,2]. DNA and histone protein modifications play a crucial role in epigenetic inheritance [3]. Dimerized ERs, as a ligand-activated transcription factor, interact with the estrogen responsive elements (EREs) on the DNA, in turn inducing or repressing gene transcription [12,13,14]. Besides their classical genomic action on EREs, ERs alter gene expression by methylating the transcription factor binding sites—cytosine and guanine rich regions in the genome, so called CpG islands—in promoter or enhancer regions. The physiological and pathophysiological relevance of E2-induced epigenetic alterations will be summarized
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