서울대학교 생물정보연구소와 생물정보학 협동과정 공동 주최로 세미나를 아래와 같이 열고자 하오니,　많은 참여 바랍니다.

일시: 2015년　4월　9일 목요일 오전　11시

연사:　박 종 훈 교수님　(숙명여자대학교 생명과학과)

장소:　서울대학교　25-1동　103호

Title:　Genome-wide methylation profiling of ADPKD identified epigenetically regulated genes associated with renal cyst development

Abstract:

Autosomal dominant polycystic kidney disease (ADPKD) is a common human genetic disease characterized by the formation of multiple fluid-filled cysts in bilateral kidneys. Although mutations in　polycystic kidney disease 1　(PKD1)　are predominantly responsible for ADPKD, the focal and sporadic property of individual cystogenesis suggests another molecular mechanism such as epigenetic changes. To determine the epigenomic alterations in ADPKD and their functional relevance, ADPKD and non-ADPKD individuals were analyzed by unbiased methylation profiling genome-wide and compared with their expression data. Intriguingly,　PKD1　and other genes related to ion transport and cell adhesion were hypermethylated in gene-body regions, and their expressions were downregulated in ADPKD, implicating epigenetic silencing as the key mechanism underlying cystogenesis. Especially, in patients with ADPKD,　PKD1　was hypermethylated in gene-body region and it was associated with recruitment of methyl-CpG-binding domain 2 (MBD2) proteins. Moreover, treatment with DNA methylation inhibitors retarded cyst formation of Madin-Darby Canine Kidney (MDCK) cells, accompanied with the upregulation of　Pkd1　expression. These results are consistent with previous studies that knock-down of　PKD1　was sufficient for cystogenesis. Therefore, our results reveal a critical role for hypermethylation of　PKD1　and cystogenesis-related regulatory genes in cyst development, suggesting epigenetic therapy as a potential treatment for ADPKD.