Reprogramming factor expression initiates widespread targeted chromatin remodeling.
Reprogramming factor expression initiates widespread targeted chromatin remodeling.
复制标题
重编程因子表达引发了广泛的靶向染色质重塑。
DOI：
10.1016/j.stem.2010.12.001
复制
发表时间：
2011-01-07
期刊：
影响因子：
23.9
通讯作者：
Meissner A
中科院分区：
文献类型：
--
作者：
Koche RP;Smith ZD;Adli M;Gu H;Ku M;Gnirke A;Bernstein BE;Meissner A
尽管在表征转录因子驱动的体细胞对诱导多能茎（IPS）细胞状态的重新编程方面的进展迅速，但仍然存在许多机械性问题。为了深入了解重编程过程中最早的事件，我们系统地分析了离散分区数量后早期因素诱导过程中发生的转录和表观遗传变化。我们在超过一千个基因座中观察到了构型组蛋白修饰的快速，全基因组的快速变化，包括大型多能与多能相关的基因启动子和增强子。相比之下，抑制性H3K27me3修饰的模式在很大程度上保持不变，除了聚焦耗竭特别是在获得H3K4甲基化的位置。这些染色质调节事件先于相应基因座内的转录变化。我们的数据提供了对异位重编程因素的早期，有组织和人口的表观遗传反应的证据，这些反应阐明了重新编程过程中某些事件的时间顺序。
Despite rapid progress in characterizing transcription factor-driven reprogramming of somatic cells to an induced pluripotent stem (iPS) cell state, many mechanistic questions still remain. To gain insight into the earliest events in the reprogramming process, we systematically analyzed the transcriptional and epigenetic changes that occur during early factor induction after discrete numbers of divisions. We observed rapid, genome-wide changes in the euchromatic histone modification, H3K4me2, at more than a thousand loci including large subsets of pluripotency-related gene promoters and enhancers. In contrast, patterns of the repressive H3K27me3 modification remained largely unchanged except for focused depletion specifically at positions where H3K4 methylation is gained. These chromatin regulatory events precede transcriptional changes within the corresponding loci. Our data provide evidence for an early, organized, and population-wide epigenetic response to ectopic reprogramming factors that clarifies the temporal order of certain events during reprogramming.
登录
查看更多内容
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hanna JH;Saha K;Jaenisch R
通讯作者：
Jaenisch R
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
64.5
作者：
Rahl PB;Lin CY;Seila AC;Flynn RA;McCuine S;Burge CB;Sharp PA;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Marson A;Levine SS;Cole MF;Frampton GM;Brambrink T;Johnstone S;Guenther MG;Johnston WK;Wernig M;Newman J;Calabrese JM;Dennis LM;Volkert TL;Gupta S;Love J;Hannett N;Sharp PA;Bartel DP;Jaenisch R;Young RA
通讯作者：
Young RA