文档介绍：1
DNA methylation
DNA***化功能
A few data
human genome :about 28 milion CpGs
60–80% are generally methylated.
Less than 10% of CpGs occur in CG-dense regions that are termed CpG islands;
Half of CGI occur at gene body.
A few knowledge
conserved enzymes
DNA methyltransferase 1 (DNMT1): DNA methylation maintenance
DNMT3A and DNMT3B:de novo methylation
DNMT3L:is a catalytically inactive homologue of DNMT3A and DNMT3B
:thymidine DNA glycosylase (TDG)
ten eleven translocation methylatosine dioxygenase(TET)
activation-induced cytodine deaminase(AID)
The many roles of DNA methylation
DNMT1
DNMT3A/B
Marking active regulatory elements
TF
Stadler et al, Nature, 2011
Imprinting
♀
♂
Brandeis et al, EMBO J, 1993
Alternative promoter regulation
Maunakea et al, Nature, 2010
Silencing of repeats
Alu/LINE/SINE
Walsh et al, Nat ics, 1998
Gene silencing
Naveh-Many and Cedar, PNAS, 1981
Cytosine
Methyl-cytosine
Known features of DNA methylation in mammals
FUNCTIONS
转录起始位点的***化:有CpG岛的模式,没有CpG岛的模式
Gene body的***化
增强子的***化
绝缘子的***化
Patterns at CpG island transcription start sites
大多数的CGIs保持不***化的状态。当在活跃的TSS有CGIs时,他们的启动子区域往往有NDRs(核小体贫乏区域),,和H3K4me3。CGI启动子能够被很多的机制所抑制,比如,myogenic differentiation 1 (MYOD1) or paired box 6 (PAX6)b蛋白,被抑制的启动子TSS区有核小体以及H3K27me3.
许多被抑制的基因同样存在CGIs的***化。这些被***化的启动子区域的CGIs大多数都是长时期的稳定的抑制状态。(例如,印记基因)
Patterns at non-CpG-island TSSs
-poor时,表达的基因往往是未***化的,而不表达的基因往往是***化的。比如OCT4 and NANOG promoters。
,发现***化和表达上没有负相关,但是在08年重分析又发现这个负相关的规律是存在。
***化是表达沉默的原因,还是结果。