差异甲基化区
差异甲基化区（英語：Differentially methylated regions，DMRs）指在多种样本（组织、细胞、个体等）中基因组里甲基化状态不相同的区域，被看作为可能参与基因转录水平调控的功能性区域。在多种组织中鉴定DMRs（T-DMRs）综合考察了人类组织中表观遗传学的差异[1]。癌症与正常样品间的DMRs（C-DMRs）展示出癌症中甲基化缺失情况[2]。众所周知，DNA甲基化与细胞分化及增殖有关[3]，现找到发育阶段（D-DMRs[4]）及重编程阶段（R-DMRs[5]）中存在的许多DMRs。此外还存在着个体内DMRs（Intra-DMRs），这种DMRs在给定的个体中随着年龄的增长而在全局DNA甲基化过程中发生纵向改变[6]。也有个体间DMRs（Inter-DMRs），这种DMRs在不同个体间存在差异甲基化类型[7]。
鉴定差异甲基化区的工具 编辑
QDMR（定量差异甲基化区）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]
参考文献 编辑
- ^ 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.
