Dynamic regulation of estrogen receptor-alpha gene expression in the brain: A role for promoter methylation?

Melinda E. Wilson, Jenne M. Westberry, Amanda K. Prewitt

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations


Estrogen has long been known to play an important role in coordinating the neuroendocrine events that control sexual development, sexual behavior and reproduction. Estrogen actions in other, non-reproductive areas of the brain have also been described. It is now known that estrogen can also influence learning, memory, and emotion and has neurotrophic and neuroprotective properties. The actions of estrogen are largely mediated through at least two intracellular estrogen receptors. Both estrogen receptor-alpha and estrogen receptor-beta are expressed in a wide variety of brain regions. Estrogen receptor-alpha (ERα), however, undergoes developmental and brain region-specific changes in expression. The precise molecular mechanisms that regulate its expression at the level of gene transcription are not well understood. Adding to the complexity of its regulation, the estrogen receptor gene contains multiple promoters that drive its expression. In the cortex in particular, the ERα mRNA expression is dynamically regulated during postnatal development and again following neuronal injury. Epigenetic modification of chromatin is increasingly being understood as a mechanism of neuronal gene regulation. This review examines the potential regulation of the ERα gene by such epigenetic mechanisms.

Original languageEnglish
Pages (from-to)375-385
Number of pages11
JournalFrontiers in Neuroendocrinology
Issue number3
StatePublished - Jun 2008

Bibliographical note

Funding Information:
This work cited from our laboratory was supported by a COBRE Grant P20 RR15592 from the National Center for Research Resources (NCRR), R01 HL073693 (M.E.W.) and American Heart Association Predoctoral Fellowship 0615231B (A.K.P.).


  • Cortex
  • DNA methylation
  • Development
  • Estrogen
  • Estrogen receptor
  • Stroke

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems


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