DNA甲基化在通过其对基因表达的效应来保持细胞身份中扮演重要角色。5'启动子的甲基化抑制基因表达，而基因内的DNA甲基化（即甲基化过程发生在一个基因体本身的内部）作用的研究却不是很多，仍然存在争议。
现在，一个基于测序技术的、来自人脑的下一代DNA甲基化图已构建成功，其覆盖面达到前所未有的程度。将这幅图与小鼠和人的组蛋白甲基化的脑组织Chip-seq及基因表达结合起来，凸显了基因内甲基化在调控基因体内的组织特异性启动子中所起的一个主要作用以及在5'启动子中所起的一个次要作用（其作用之小出乎意料）。 (生物谷Bioon.net)
生物谷推荐原文出处：
Nature doi:10.1038/nature09165
Conserved role of intragenic DNA methylation in regulating alternative promoters
Alika K. Maunakea,Raman P. Nagarajan,Mikhail Bilenky,Tracy J. Ballinger,Cletus D’Souza,Shaun D. Fouse,Brett E. Johnson,Chibo Hong,Cydney Nielsen,Yongjun Zhao,Gustavo Turecki,Allen Delaney,Richard Varhol,Nina Thiessen,Ksenya Shchors,Vivi M. Heine,David H. Rowitch,Xiaoyun Xing,Chris Fiore,Maximiliaan Schillebeeckx,Steven J. M. Jones,David Haussler,Marco A. Marra,Martin Hirst,Ting Wang& Joseph F. Costello
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. The CpG islands in all three locations overlapped with RNA markers of transcription initiation, and unmethylated CpG islands also overlapped significantly with trimethylation of H3K4, a histone modification enriched at promoters16. The general and CpG-island-specific patterns of methylation are conserved in mouse tissues. An in-depth investigation of the human SHANK3 locus17, 18 and its mouse homologue demonstrated that this tissue-specific DNA methylation regulates intragenic promoter activity in vitro and in vivo. These methylation-regulated, alternative transcripts are expressed in a tissue- and cell type-specific manner, and are expressed differentially within a single cell type from distinct brain regions. These results support a major role for intragenic methylation in regulating cell context-specific alternative promoters in gene bodies.
