2018 Fiscal Year Final Research Report
Elucidation of an epigenetic hierarchy mediated by CXXC proteins
| Project/Area Number |
15H05602
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Genetics/Chromosome dynamics
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
ITO SHINSUKE 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 (50612115)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Keywords | エピジェネティクス / CpGアイランド / 遺伝子発現抑制 |
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| Outline of Final Research Achievements |
The majority of mammalian gene promoters are associated with specialized genomic regions called CpG islands (CGI) that contribute to regulation of gene expression by attracting specific histone modifying enzymes. However, the precise mechanisms by which how CXXC domain-containing proteins, CXXC1 and KDM2B specifically recognize their target CGIs remain poorly understood. Therefore, in this project, we aim to understand the detailed mechanisms to establish epigenetic modifications at specific loci.Here, by using biochemical approach combined with a mice genetic study, we demonstrated CXXC1 and KDM2B specifically recruit associated complex and induce epigenetic modifications. We also revealed Polycomb-proteasome axis could play a critical role in specification of recruitment of CXXC-associated complexes. Therefore, ubiquitin-proteasome system is involves in polycomb-mediated transcriptional regulation and could serve as a gatekeeper for ensuring a proper epigenetic landscape of CGI.
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| Free Research Field |
ゲノム動態
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| Academic Significance and Societal Importance of the Research Achievements |
エピジェネティック修飾は、個体発生 ・分化の過程において時空間的に厳格な遺伝子発現制御を行う上で重要な役割を果たしている。このエピジェネティック修飾は、その重要さ故に、エピジェネティック修飾の破綻は、様々な疾患の発症に繋がるため、エピジェネティック修飾が如何に導入されるかを詳細に理解することは極めて重要である。とりわけ、CpGアイランドのエピジェネティック修飾の異常が様々な疾患やがんにて報告されている。したがって、本研究成果は、エピジェネティック修飾の忠実に導入するメカニズムの一端を明らかにするものであり、その異常が疾患発症の原因になる可能性をもつとかんがえる。
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