Analysis of chromatin network involving centromere functional components

2015 Fiscal Year Final Research Report

• Project Area: Functions of non-coding DNA region for genome integrity
• Project/Area Number: 23114008
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kazusa DNA Research Institute
• Principal Investigator: Masumoto Hiroshi 公益財団法人かずさDNA研究所, 先端研究部, 室長 (70229384)
• Co-Investigator(Renkei-kenkyūsha): NAKANO Megumi (公益財団法人)かずさDNA研究所, 研究員 (50542825) ; OHZEKI Jun-ichirou (公益財団法人)かずさDNA研究所, 研究員 (30514088)
• Research Collaborator: OKAZAKI Kouei (公益財団)かずさDNA研究所, 主任研究員 (70213923) ; KUGOU Kazuto (公益財団)かずさDNA研究所, 研究員 (60554425)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 非コードDNA / サテライトDNA / セントロメア / ヘテロクロマチン / CENP-A / ヒストンアセチル化酵素 / CENP-B / Suv39H1

Outline of Final Research Achievements

We examined chromatin assembly network at centromeres by synthetically generating functional structures using synthetic repetitive DNAs and combination of various fusion protein tetherings. Results indicated that CENP-C and CENP-I are key connecting factors for the functional kinetochore assembly and an epigenetic CENP-A chromatin replenishment. Further, we identified the interaction between M18BP1, a CENP-A assembly factor just downstream of CENP-C, and acetyltransferase KAT7/HBO1/MYST2. Knocking out KAT7 in HeLa cells reduced centromeric CENP-A levels. Acetylation of histone H3K14 induced by KAT7 provides competence for histone turnover/exchange activity and prevents Suv39h1-mediated heterochromatin invasion into centromeres. And thus, this reaction promotes HJURP mediated CENP-A replenishment on the repetitive DNA.

Free Research Field

分子生物学