Analysis of action mechanism of endocrine-disruptors targeting epigenetic memory

2015 Fiscal Year Final Research Report

• Project/Area Number: 25340046
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Shizuoka University
• Principal Investigator: YAMAUCHI Kiyoshi 静岡大学, グリーン科学技術研究所, 教授 (50201827)
• Co-Investigator(Kenkyū-buntansha): ISHIHARA Akinori 静岡大学, 理学部, 講師 (70432193) ; NISHIYAMA Norihito 福島県立医科大学, 医学部, 講師 (10315666)
• Co-Investigator(Renkei-kenkyūsha): MOCHIZUKI Kazuki 山梨大学, 生命環境学部, 准教授 (80423838)
• Research Collaborator: OTSUKA Shunsuke ; IZUMI Yushi ; KASAI Kentaro ; TAMAOKI Keiji
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 甲状腺ホルモン / ホルモン応答遺伝子 / 撹乱化学物質 / エピジェネティック作用 / ヒストン修飾 / RNAポリメラーゼII

Outline of Final Research Achievements

Thyroid hormones (THs) play important roles in growth, development, differentiation, and metabolism in vertebrates. To elucidate molecular mechanisms by which environmental chemicals exert TH-disrupting activity, we investigated their effects on the histone and RNA polymerase II (RNAPII) modifications and DNA methylation status in two direct TH-response genes in amphibian TH-responsive cultured cells. For both genes, TH enhanced the amounts of gene transcripts and increased the amounts of epigenetic marks of transcription activation. Treatment with the chemicals reduced the amounts of the gene transcript and suppressed some of the T3-induced epigenetic marks. However, the 5' regulatory region remained to be hypermethylated even with exposure to TH. Our results demonstrate that the chemicals affect TH-induced histone and RNAPII modifications in direct TH-response genes, in somewhat target gene-dependent and chemical-specific manners.

Free Research Field

環境内分泌学