[대학원 생명과학과 세미나 안내]
연사 : 구자욱 박사(한국뇌연구원(KBRI))
연제 : Epigenetic basis of Bdnf gene suppression by drugs of abuse in the ventral tegmental area
일시 : 2016년 12월 9일 (금) 오후 4시
장소 : 하나과학관 A동 109호
초청교수 : 윤봉준 교수
Abstract
Brain-derived neurotrophic factor (BDNF) plays a crucial role in modulating neural and behavioral plasticity to drugs of abuse. Here, we demonstrate a persistent down-regulation of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response to chronic opiate exposure, which is mediated by specific epigenetic modifications at the corresponding Bdnf gene promoters. Exposure to chronic morphine increases stalling of RNA polymerase II at these Bdnf promoters in VTA and alters permissive and repressive histone modifications and occupancy of their regulatory proteins at the specific promoters. Furthermore, we show that morphine suppresses binding of phospho-CREB (cAMP response element binding protein) to Bdnf promoters in VTA, which results from enrichment of trimethylated H3K27 at the promoters. These studies reveal novel epigenetic mechanisms of morphine-induced molecular and behavioral neuroadaptations.