Development of a translational correction method for resolutional improvement of nucleosome maps

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05505
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Shimane University
• Principal Investigator: Kato Hiroaki 島根大学, 学術研究院医学・看護学系, 准教授 (40548418)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ヌクレオソーム / ヒストン / 転写 / エピジェネティクス

Outline of Final Research Achievements

By analyzing the digestion preference of micrococcal nuclease (MNase), we successfully extracted nucleosome positions of high accuracy from MNase-seq data sets. These nucleosomes exhibited a fine pattern of WW/SS dinucleotides, which is comparable to those determined by chemical mapping methods. Comparison of MNase-seq-based and chemical mapping-based nucleosomes revealed that even chemical mapping methods have histone mutant-specific cleavage biases. Analysis of genes with a hybrid chemical model suggested that +1 nucleosome DNA has a high affinity to histones especially in the promoter-proximal half. Transcription start sites determined by CAGE-seq were located in the promoter-proximal side of +1 nucleosome. Analysis of promoter sequences identified two types of TSS in yeast: one has adenine at -8 nucleotide position, and the other one that are related to the rotational setting of +1 nucleosomes.

Free Research Field

エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

今日、様々な生体分子の振る舞いは構造生物学によって高解像度に明らかにされつつある。ただし、その多くは人工的に再構成された複合体を対象としており、自然条件における実際の分子の振る舞いまで網羅することが難しい。例えばヌクレオソームの関わる再構成系では特別なDNA配列が使用される傾向があり、自然配列を網羅的に評価できないので、タンパク質複合体と自然DNA配列との関係性については謎に包まれている。
塩基対解像度でヌクレオソーム配置に関わるDNA配列の特徴を明らかにしようとする本研究は、自然配列を対象とする点で特徴的であり、構造生物学の不足を補う視点を提供できる。このため、今後の進展が期待される。