Possible involvement of DNA methylation in NKCC1 gene expression during postnatal development and in response to ischemia

摘要: In CNS, GABA(A) receptor-mediated responses switch from depolarization to hyperpolarization during postnatal development. This is mediated by developmental down-regulation of inwardly directed Na(+)-K(+)-2Cl(-) co-transporter type 1 (NKCC1) and up-regulation outwardly K(+)-Cl(-) 2. While several factors have been shown regulate 2 expression, little known about the mechanisms which expression NKCC1 regulated Here, we report a novel epigenetic mechanism underlying regulation gene in rat cerebral cortex. vitro DNA methylation promoter region, contains high density cytosine-phosphodiester-guanine islands, significantly decreased mRNA, degree region increased addition, treatment with 5-aza-2'-deoxycytidine, specific methyltransferase inhibitor, elicited an increase mRNA protein cortical slice cultures. Focal ischemic injury induced occlusion middle artery led re-expression even mature The injured cortex was related decrease status region. Our results indicate that mechanisms, such as methylation, might be involved development well under pathological conditions.