Ragulating chromatin structures by manipulating chromatin loops

2015 Fiscal Year Final Research Report

• Project/Area Number: 25650014
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: MASAI Hisao 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 副所長 (40229349)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: Rif1タンパク質 / クロマチンループ / 核内染色体構造 / 複製タイミング / グアニン4重鎖構造 / 核膜

Outline of Final Research Achievements

We try to develop a novel method by which to manipulate chromatin loop structures by using a conserved nuclear protein, Rif1. Rif1 was shown to regulate DNA replication timing domains through facilitating formation of chromatin loops. Fission yeast Rif1 binds specifically to G-quadruplex (G4) structures through its C-terminal 271 aa segment and conserved amino acids near its C-terminus are required for both its DNA binding and oligomerization. Overexpression of Rif1 in fission yeast induced aberrant chromatin structures and growth inhibition. Growth inhibition did not require its PP1 binding but required DNA binding activity. Based on the target preference of Rif1 protein, we are now manipulating chromatin structures and activities by introducing high-affinity Rif1 target G4 sequences at specific locations on the chromosomes.

Free Research Field

分子生物学