2018 Fiscal Year Final Research Report
Cross-lineage analysis of the genomic binding sites of a transcriptional repressor BLIMP1 with a ChIP-sea method for small number of cells
| Project/Area Number |
16H04720
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Genome biology
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| Research Institution | Nara Medical University (2018)
Kyoto University (2016-2017) |
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Principal Investigator |
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| Research Collaborator |
Mitani Tadahiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | BLIMP1 / ChIP-seq / 微量解析 / 生殖細胞 / 小腸 / 視細胞 / 形質芽球 |
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| Outline of Final Research Achievements |
Single transcription factors, including repressive transcriptional regulators, often play critical roles in development of many cell lineages, of which precise mechanisms are elusive. In this study, using the ChIP-seq method that I have developed, I determined BLIMP1-binding sites in primordial germ cell-like cells (PGCLCs), E12.5 PGCs (germ line), E16.5 embryonic intestinal epithelium (endoderm), perinatal photoreceptor precursors (ectoderm), and plasma blast (mesoderm), and compared them with the gene expression dynamics during development of these cell types. Through this comparative cross-lineage approach, I discovered principles of the relationship between the features of BLIMP1 binding sites and their gene-regulatory activities (particularly, repressive activity). This is the first study that compares binding sites of a specific transcription factor during development of multiple cell lineages across germ layers (germ line and the the germ layers, 6 cell types).
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| Free Research Field |
ゲノム生物学、発生学
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| Academic Significance and Societal Importance of the Research Achievements |
個体の全細胞は単一の受精卵を起源とする。単一のゲノムが多様な機能を持ち多様な細胞を形成するためには転写因子によるゲノム制御が不可欠である。また同一の転写因子が多様な細胞種の決定に関わることもよく知られている。転写因子はゲノムに結合しても必ずしも活性を発揮するとは限らず、どのゲノム結合部位が機能を担うかは重要であるが、技術的な限界から、生体内の具体的な結合部位は不明な点が多かった。本研究の意義は、研究代表者が開発した微量解析法を用いて、生体内に存在する多系統の細胞種における重要な転写因子BLIMP1の結合部位を遺伝子発現動態と合わせて横断的に比較し、活性を持つ結合部位の特徴を抽出したことである。
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