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DNA甲基化在通過其對基因表達的效應來保持細胞身份中扮演重要角色。5'啟動子的甲基化抑制基因表達，而基因內的DNA甲基化（即甲基化過程發生在一個基因體本身的內部）作用的研究卻不是很多，仍然存在爭議。

Although it is known that the methylation of DNA in 5′ promoters suppresses gene expression, the role of DNA methylation in gene bodies is unclear1, 2, 3, 4, 5. In mammals, tissue- and cell type-specific methylation is present in a small percentage of 5′ CpG island （CGI） promoters, whereas a far greater proportion occurs across gene bodies, coinciding with highly conserved sequences5, 6, 7, 8, 9, 10. Tissue-specific intragenic methylation might reduce3, or, paradoxically, enhance transcription elongation efficiency1, 2, 4, 5. Capped analysis of gene expression （CAGE） experiments also indicate that transcription commonly initiates within and between genes11, 12, 13, 14, 15. To investigate the role of intragenic methylation, we generated a map of DNA methylation from the human brain encompassing 24.7 million of the 28 million CpG sites. From the dense, high-resolution coverage of CpG islands, the majority of methylated CpG islands were shown to be in intragenic and intergenic regions, whereas less than 3% of CpG islands in 5′ promoters were methylated.

現在，一個基于測序技術的、來自人腦的下一代DNA甲基化圖已構建成功，其覆蓋面達到的程度。將這幅圖與小鼠和人的組蛋白甲基化的腦組織Chip-seq及基因表達結合起來，凸顯了基因內甲基化在調控基因體內的組織特異性啟動子中所起的一個主要作用以及在5'啟動子中所起的一個次要作用（其作用之小出乎意料）。