2018 Fiscal Year Annual Research Report
Detecting combinatorial histone modification dynamics at single nucleosome resolution for key genes in Epithelial-Mesenchymal-Transition
| Project/Area Number |
17K18358
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
チャン レンチエン 国立研究開発法人理化学研究所, 生命医科学研究センター, 研究員 (10792137)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | chromatin / histone modification / nucleosome / single-molecule imaging / EMT / bivalent promoter / enChIP / epigenetics |
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| Outline of Annual Research Achievements |
Each human cell type has a unique function enabled by the usage of specific combinations of different parts of the genome. It is regulated at many molecular levels. Histones are critical components in nucleosomes, the fundamental genome organization unit. Multiple histone modifications can co-occur on the same nucleosome and function together through crosstalk to control gene regulation. Therefore, studying combination of histone modifications can be informative in revealing abnormal cell states during diseases. In this kakenhi research, we aimed to develop a novel single-molecule imaging method for combinatorial histone modifications at the single nucleosome resolution and applied it to understand intermediate epigenetic states for key genes during Epithelial-Mesenchymal Transition (EMT) which is relevant in cancer metastasis.
In FY2017, the progress has been made in establishing sample preparation protocol, developing the imaging system, as well as ChIP-seq profiling of EMT system. In FY2018, enChIP for enrichment of chromatin from single specific locus for single-molecule imaging was attempted; however, the noise was proved to be high for such purpose. Another route of obtaining genomic location for the nucleosome after imaging is ongoing, by integrating in situ single-molecule sequencing. On the other side, by further bioinformatics analysis of the data, we have identified a list of candidate genes with varied chromatin states in EMT. The results have been presented in several conferences.
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Research Products
(2 results)
