Genomic Targets of Nuclear Estrogen Receptors

Abstract

Estrogen influences the physiology of many target tissues in both women and men. The long-term effects of estrogen are mediated predominantly by nuclear estrogen receptors (ERs) functioning as DNA-binding transcription factors. Tissue-specific responses to estrogen therefore result from regulation of different sets of genes. However, it remains perplexing as to what regulatory sequence contexts specify distinct genomic responses. First, this review classifies estrogen response sequences in mammalian target genes. Of note, around one third of known human target genes associate only indirectly with ER, through intermediary transcription factor(s). Then, computational approaches are presented both for refining direct ER-binding sites and for formulating hypotheses regarding the overall genomic expression pattern. Surprisingly, limited evolutionary conservation of specific estrogen-responsive sites is observed between human and mouse. Finally, consideration of the cellular functions of regulated human genes suggests links between particular biological roles and specific types of estrogen response elements, although with the important caveat that only a restricted set of target genes is available. These analyses support the view that specific, hormone-driven gene expression programs can result from the interplay of environmental and cellular cues with the distinct types of estrogen-response sequences.

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

“…We have known from previous studies that E2-stimulated breast cancer cell proliferation involves ERα-mediated regulation of several key cell cycle regulatory genes (Coser et al, 2003;Ngwenya et al, 2003;O'Lone et al, 2004;Eeckhoute et al, 2006). Aberrant DNA methylation of tumor suppressor genes has been reported in many major types of cancer with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes.…”

Interleukin 3 and schizophrenia: the impact of sex and family history

“…These include the direct binding to EREs to activate transcription and indirect binding to AP-1, SP1 and GATA binding proteins to coactivate the expression of genes. 32,33 In other words, estrogen can directly and indirectly regulate the expression of ACSL6 and IL3 genes. In one report, sex-specific expression of IL3 was found in breast cancer patients.…”

Estrogen receptor β exon 3-deleted mouse: The importance of non-ERE pathways in ERβ signaling

“…It is now known that one-third of the categorized human 17β-estradiol-responsive genes are transcribed via indirect ER-DNA association through proteinprotein interactions with several transcription factors (13). Both ERα and ERβ can exert transcriptional regulation by tethering to other transcription factors such as c-Fos/c-Jun (activator protein-1, AP-1), Sp1, or NF-κB without themselves binding to EREs on DNA (13)(14)(15)(16)(17)(18). Genome landscaping has revealed that the non-ERE-dependent mode of transcription is the preferred pathway used by ERβ to regulate transcription of its target genes.…”