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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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2015: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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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 / ポリコーム / ユビキチン / 転写抑制 / 転写制御 / ゲノム / 発現制御 / CGI / CXXC |
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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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| 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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Report
(5 results)
Research Products
(14 results)
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[Journal Article] A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities.2018
Author(s)
Conway E, Jerman E, Healy E, Ito S, Holoch D, Oliviero G, Deevy O, Glancy E, Fitzpatrick DJ, Mucha M, Watson A, Rice AM, Chammas P, Huang C, Pratt-Kelly I, Koseki Y, Nakayama M, Ishikura T, Streubel G, Wynne K, Hokamp K, McLysaght A, Ciferri C, Di Croce L, Cagney G, Margueron R, Koseki H, Bracken AP.
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Journal Title
Mol Cell.
Volume: 70
Issue: 3
Pages: 408-421
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The SET1 Complex Selects Actively Transcribed Target Genes via Multivalent Interaction with CpG Island Chromatin.2017
Author(s)
Brown DA, Di Cerbo V, Feldmann A, Ahn J, Ito S, Blackledge NP, Nakayama M, McClellan M, Dimitrova E, Turberfield AH, Long HK, King HW, Kriaucionis S, Schermelleh L, Kutateladze T, Koseki H, Klose RJ.
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Journal Title
Cell Rep
Volume: 20
Issue: 10
Pages: 2313-2327
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes.2017
Author(s)
Endoh M, Endo TA, Shinga J, Hayashi K, Farcas A, Ma KW, Ito S, Sharif J, Endoh T, Onaga N, Nakayama M, Ishikura T, Masui O, Kessler BM, Suda T, Ohara O, Okuda A, Klose RJ, Koseki H.
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Journal Title
Elife
Volume: 6
Pages: 27970-27970
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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