2010 Fiscal Year Final Research Report
Elucidation of mechanisms of germ cell reprogramming and establishment of the procedure to control epigenome.
| Project/Area Number |
21780269
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
INOUE Kimiko The Institute of Physical and Chemical Research, 遺伝工学基盤技術室, 専任研究員 (70360500)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 核移植クローン / エピゲノム / 遺伝子発現 / X染色体 / H3K9me2 / DNAマイクロアレイ / Xist |
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| Research Abstract |
To improve understanding of the low efficiency of somatic cell nuclear transfer (SCNT), we performed global transcription analysis of mouse SCNT blastocysts. Many of the downregulated genes (21/39) identified in SCNT embryos were located on the X chromosome. When the downregulation of X-linked genes in SCNT embryos was corrected by using Xist-deficient donor cells, the birth rates increased 8- to 9-fold. Thus, SCNT may be significantly improved by correcting epigenetic errors specific for SCNT.
In the next series of experiments, to understand the cause of consistent downregulation in the region of A7.2 and F3 on X chromosome (XqA7.2/F3) in SCNT blastocysts, we analyzed repressive modification, dimethylation of histone H3 lysine 9 (H3K9me2), with chromatin immunoprecipitation-on-chip data from cumulus cells. The results showed that H3K9me2 was broadly enriched in XqA7.2/F3 and formed tissue-specific blocks called as large organized chromatin K9 modification (LOCKs). These data suggested that downregulation of XqA7.2/F3 was caused by failure of reprogramming of LOCKs after nuclear transfer.
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[Journal Article] Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer2010
Author(s)
Inoue K, Kohda T, Sugimoto M, Sado T, Ogonuki N, Matoba S, Shiura H, Ikeda R, Mochida K, Fujii T, Sawai K, Otte A.P,Tian C., X, Yang X,Ishino F, Abe K, aOgura A
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Journal Title
Science. 330
Pages: 496-499
Peer Reviewed
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[Remarks] ホームページ等
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