Estradiol-Induced Epigenetically Mediated Mechanisms and Regulation of Gene Expression

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.

Heat Shock Factor 1 (HSF1) as a new tethering factor for ESR1 supporting its action in breast cancer

“…Transcriptional activation by ESR1 is a multistep process modulated by coactivators and corepressors. Cofactors interact with the receptor in a ligand-dependent manner and are often part of large multiprotein complexes that control transcription by recruiting components of the basal transcription machinery, regulating chromatin structure, and/or modifying histones (Welboren et al, 2009) (Kovács et al, 2020) (Pescatori et al, 2021). Liganded ESR1 may bind directly to DNA (to ERE), and indirectly via tethering to other transcription factors such as FOS/JUN (AP1), STATs, ATF2/JUN, SP1, NFκB (Björnström and Sjöberg, 2005) (Welboren et al, 2009) (Heldring et al, 2011).…”

Upregulation of LINC00511 expression by DNA hypomethylation promotes the progression of breast cancer

“…PRC2, polycomb complex 2) and different protein complexes (PRC2. NurD, Nucleosome Remodeling Deacetylase) to promote DNA methylation in the promoter or enhancer region (22). ER deficiency enhance the transcriptional activity of LING00511 (23).…”

Revisiting the Impact of Local Leptin Signaling in Folliculogenesis and Oocyte Maturation in Obese Mothers

“…More recently, ERβ was shown to mediate the expression of Junction Adhesion Molecule Like (Jaml) , a gene needed for the communication between GC and oocyte, as well as other genes Polypeptide N-Acetylgalactosaminyltransferase (Galnt) 6 or Egf receptor (Egfr) , necessary for preovulatory follicle development [ 87 ]. It is noteworthy that detailed E2 genomic actions in antral follicle development have been described elsewhere [ 88 ]. Nonetheless, E2 is also known to exert non-genomic actions through the membrane receptor, the G protein-coupled estrogen receptor (GPER) 1 [ 81 ].…”