2012 Fiscal Year Final Research Report
General principle and importance of organization of chromosome structures during mammalian development and cell differentiation
| Project/Area Number |
22380188
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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 |
Applied molecular and cellular biology
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| Research Institution | Mie University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SUGIMURA Kazuto 三重大学, 大学院・医学系研究科, 助教 (90452226)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 染色体 / ゲノム / 複製フォーク / クロマチン / エピジェネティクス / DNAメチル化 / DNA損傷 |
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| Research Abstract |
In mammals, DNA methylation is an important epigenetic mark that is associated with chromosome construction. Using a DNA methylation inhibitor, we found that reduced levels of DNA methylation were associated with the activation of transcription from centromere regionsand a shift in replication timing of the pericenromeric regions from middle/late S to early S phase through depositing histone H3.3 on pericenromeric heterochromatin prior to the accumulation of the euchromatic histone modification, suggesting that DNA methylation is essential for proper organization of pericentromeric heterochromatin in differentiated mouse cells. We also found that DNA methyltransferase 1 knockdown or inhibition causes replication fork stalling and replication-associated DNA damages. We propose that replication stress in the course of passive DNA demethylation could be a source of spontaneous mutations and genomic instability during tumorigenesis and aging.
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[Journal Article] The histone chaperone facilitates chromatin transcription (FACT) protein maintains normal replication fork rates
Author(s)
T. Abe, K.Sugimura, Y. Hosono, Y. Takami, M. Akita, A. Yoshimura, S. Tada, T. Nakayama, H. Murofushi, K. Okumura, S. Takeda, M. Horikoshi, M. Seki, T
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Journal Title
Enomoto. J. Biol. Chem.
Volume: 286(35)
Pages: 30504-30512
DOI
Peer Reviewed
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