Rules governing the mechanism of epigenetic reprogramming memory.
Rules governing the mechanism of epigenetic reprogramming memory.
复制标题
表观遗传重编程记忆机制的规则。
作者：
Phuc;Daniela Gerovska;H. Schöler;M. Araúzo
目标
揭示了调节重新编程内存的机制。
材料与方法
我们建立了在单个CPGS上寻找DNA甲基化体细胞记忆位点(SMs)的计算程序，并将它们与基因组学、表观基因组学、转录组学和印记信息相结合。
结果与结论
重新编程记忆在低甲基化区域的后期持续存在。相反，与低甲基化相反，高甲基化的SMS发生在动态染色质区域中与活性转录位点重叠的进化保守位置。表观遗传记忆的分子起源是源细胞转录因子的表达，保护常染色质中低甲基化的SMS不受从头甲基化的影响，使诱导的多能干细胞(IPS)中的源细胞谱系特异性基因座不完全沉默。不同于源细胞谱系的谱系特异性基因中的位点在异染色质区域保持高甲基化，变得永久沉默。SMSS通过两种机制导致iPS细胞和胚胎干细胞的差异表达：表观遗传/表达记忆规则，DNA非重编程甲基化状态与染色质状态相结合，诱导差异表达的基因。“印记控制”，印记控制区DNA甲基化状态的改变导致印记基因的差异表达。
AIM
Disclosing the mechanisms that regulate reprogramming memory.
MATERIALS & METHODS
We established computational procedure to find DNA methylation somatic memory sites (SMSs) at single CpGs and integrated them with genomics, epigenomics, transcriptomics and imprinting information.
RESULTS & CONCLUSION
Reprogramming memory persists at late passages in low methylated regions. Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary conserved sites overlapping active transcription loci in dynamic chromatin regions. The epigenetic-memory molecular origin is the expression of source-cell transcription factors protecting hypomethylated SMSs in euchromatin from de novo methylation, keeping source-cell lineage-specific loci in induced pluripotent stem (iPS) cells incompletely silenced. Sites in lineage-specific genes of different-from-those-of-the-source-cell lineages remain hypermethylated in heterochromatin regions becoming permanently silenced. SMSs cause differential expression between iPS cells and embryonic stem cells through two mechanisms: 'epigenetic/expression memory rule', the DNA unreprogramming methylation status coupled with chromatin states induces differentially expressed genes. 'Imprinting control', the change of DNA methylation status in imprinting control regions induces differential expression of imprinted genes.
登录
查看更多内容
影响因子：
7
作者：
Siepel, A;Bejerano, G;Haussler, D
通讯作者：
Haussler, D
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
7
作者：
Choufani, Sanaa;Shapiro, Jonathan S.;Weksberg, Rosanna
通讯作者：
Weksberg, Rosanna
影响因子：
4
作者：
Wilson, Kitchener D.;Venkatasubrahmanyam, Shivkumar;Wu, Joseph C.
通讯作者：
Wu, Joseph C.