差異甲基化區
差異甲基化區（英語：Differentially methylated regions，DMRs）指在多種樣本（組織、細胞、個體等）中基因組里甲基化狀態不相同的區域，被看作為可能參與基因轉錄水平調控的功能性區域。在多種組織中鑑定DMRs（T-DMRs）綜合考察了人類組織中表觀遺傳學的差異[1]。癌症與正常樣品間的DMRs（C-DMRs）展示出癌症中甲基化缺失情況[2]。眾所周知，DNA甲基化與細胞分化及增殖有關[3]，現找到發育階段（D-DMRs[4]）及重編程階段（R-DMRs[5]）中存在的許多DMRs。此外還存在著個體內DMRs（Intra-DMRs），這種DMRs在給定的個體中隨著年齡的增長而在全局DNA甲基化過程中發生縱向改變[6]。也有個體間DMRs（Inter-DMRs），這種DMRs在不同個體間存在差異甲基化類型[7]。
鑑定差異甲基化區的工具
編輯QDMR（定量差異甲基化區）is a quantitative approach to quantify methylation difference and identify DMRs from genome-wide methylation profiles by adapting Shannon entropy (https://web.archive.org/web/20151023040525/http://bioinfo.hrbmu.edu.cn/qdmr/). The platform-free and species-free nature of QDMR makes it potentially applicable to various methylation data. This approach provides an effective tool for the high-throughput identification of the functional regions involved in epigenetic regulation. QDMR can be used as an effective tool for the quantification of methylation difference and identification of DMRs across multiple samples.[8]
參考文獻
編輯- ^ Rakyan, VK; Down, TA; Thorne, NP; Flicek, P; Kulesha, E; Gräf, S; Tomazou, EM; Bäckdahl, L; Johnson, N; Herberth, M; Howe, KL; Jackson, DK; Miretti, MM; Fiegler, H; Marioni, JC; Birney, E; Hubbard, TJ; Carter, NP; Tavaré, S; Beck, S. An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome research. 2008 Sep, 18 (9): 1518–29. PMC 2527707
. PMID 18577705. doi:10.1101/gr.077479.108.
- ^ Irizarry, RA; Ladd-Acosta, C; Wen, B; Wu, Z; Montano, C; Onyango, P; Cui, H; Gabo, K; Rongione, M; Webster, M; Ji, H; Potash, JB; Sabunciyan, S; Feinberg, AP. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nature genetics. 2009 Feb, 41 (2): 178–86. PMC 2729128 . PMID 19151715. doi:10.1038/ng.298.
- ^ Reik, W; Dean, W; Walter, J. Epigenetic reprogramming in mammalian development. Science. 2001-08-10, 293 (5532): 1089–93. PMID 11498579. doi:10.1126/science.1063443.
- ^ Meissner, A; Mikkelsen, TS; Gu, H; Wernig, M; Hanna, J; Sivachenko, A; Zhang, X; Bernstein, BE; Nusbaum, C; Jaffe, DB; Gnirke, A; Jaenisch, R; Lander, ES. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008-08-07, 454 (7205): 766–70. Bibcode:2008Natur.454..766M. PMC 2896277 . PMID 18600261. doi:10.1038/nature07107.
- ^ Doi, A; Park, IH; Wen, B; Murakami, P; Aryee, MJ; Irizarry, R; Herb, B; Ladd-Acosta, C; Rho, J; Loewer, S; Miller, J; Schlaeger, T; Daley, GQ; Feinberg, AP. Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nature genetics. 2009 Dec, 41 (12): 1350–3. PMC 2958040 . PMID 19881528. doi:10.1038/ng.471.
- ^ Bjornsson, HT; Sigurdsson, MI; Fallin, MD; Irizarry, RA; Aspelund, T; Cui, H; Yu, W; Rongione, MA; Ekström, TJ; Harris, TB; Launer, LJ; Eiriksdottir, G; Leppert, MF; Sapienza, C; Gudnason, V; Feinberg, AP. Intra-individual change over time in DNA methylation with familial clustering. JAMA : the journal of the American Medical Association. 2008-06-25, 299 (24): 2877–83. PMC 2581898 . PMID 18577732. doi:10.1001/jama.299.24.2877.
- ^ Bock, C; Walter, J; Paulsen, M; Lengauer, T. Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping. Nucleic acids research. 2008 Jun, 36 (10): e55. PMC 2425484 . PMID 18413340. doi:10.1093/nar/gkn122.
- ^ Zhang, Y; Liu, H; Lv, J; Xiao, X; Zhu, J; Liu, X; Su, J; Li, X; Wu, Q; Wang, F; Cui, Y. QDMR: a quantitative method for identification of differentially methylated regions by entropy. Nucleic acids research. 2011 May, 39 (9): e58. PMC 3089487 . PMID 21306990. doi:10.1093/nar/gkr053.
