Regulation of XXXX receptor gene expression: new insights and novel mechanisms.

@entity1 @entity1782 @entity4998 @entity0 @entity2931 @entity2500 @entity53 @entity1783 @entity8251 @entity5498 @entity528
@entity53 is a pleiotropic hormone with organisational, activational and protective actions in both male and female mammals. It is responsible for numerous aspects of brain development, including @entity4998 . The organisational effects of early @entity2931 exposure are essential for long-lasting cognitive and behavioural functions. @entity53 mediates its effects through several intracellular or membrane-associated receptor proteins. In the rodent cerebral cortex, @entity2931 receptor (ER) expression, as demonstrated by hormone binding studies, is high early in postnatal life and declines precipitously as the animal approaches puberty. This decline is caused by a decreased expression of @entity1782 mRNA. An understanding of the mechanisms involved in the regulation of @entity1782 gene expression is critical for understanding the developmental as well as postpubertal expression of the ER. Despite recent data indicating the current hormone replacement therapies can be detrimental in older @entity1 , numerous animal studies have shown that the endogenous @entity2931 , @entity53 , is neuroprotective. Specifically, low levels of @entity53 protect the cortex from cell death caused by @entity2500 ( @entity2500 ). The attenuation of cell death by @entity53 in this model is mediated through an @entity1782 -dependent mechanism. To this end, @entity1782 expression is rapidly increased after @entity2500 , suggesting a return to the developmental programme of gene expression within neurones. One mechanism of suppressing gene expression is by the epigenetic modification of the promoter regions, which results in gene silencing. Of the epigenetic modifications utilised by cells, DNA methylation has been intensively studied as a mechanism by which genes are both permanently and reversibly silenced. Little is known about the mechanisms of ER gene regulation in the brain; however, in @entity0 cells, both @entity1782 and @entity1783 are down-regulated by promoter methylation, and subsequent binding of the @entity5498 -CpG-binding protein, @entity8251 . Data from our laboratory demonstrate that the promoters of the @entity1782 gene are also methylated during development and after @entity528 , suggesting a role of DNA methylation in regulating ER expression in the brain.
