Polycomb-repressed genes have permissive enhancers that initiate reprogramming.
Polycomb-repressed genes have permissive enhancers that initiate reprogramming.
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DOI：
10.1016/j.cell.2011.10.040
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发表时间：
2011-12-09
期刊：
影响因子：
64.5
通讯作者：
Jones PA
中科院分区：
文献类型：
--
作者：
Taberlay PC;Kelly TK;Liu CC;You JS;De Carvalho DD;Miranda TB;Zhou XJ;Liang G;Jones PA
被Polycomb和H3 K27 me 3抑制的关键调控基因在正常分化和诱导重编程期间变得活跃。使用MYOD 1的良好表征的增强子/启动子对作为模型，我们已经确定了增强子在重编程中的关键作用。我们观察到一个意想不到的核小体耗尽区（NDR）在H3 K4 me 1富集的增强子，转录调节最初结合，导致随后的变化，在同源启动子的染色质。外源性Myod 1通过首先在增强子处结合而激活其自身的转录，从而在相关MYOD 1启动子处产生NDR和转录允许染色质。外源性OCT 4也首先结合到允许MYOD 1增强子，但对同源启动子具有不同的作用，其中单价H3 K27 me 3标记被转化为干细胞特征性的二价状态。在全基因组范围内，高百分比的Polycomb靶标与许可状态下的推定增强子相关，这表明它们可能为细胞命运重编程的启动提供广泛的途径。
Key regulatory genes, suppressed by Polycomb and H3K27me3, become active during normal differentiation and induced reprogramming. Using the well-characterized enhancer/promoter pair of MYOD1 as a model, we have identified a critical role for enhancers in reprogramming. We observed an unexpected nucleosome depleted region (NDR) at the H3K4me1-enriched enhancer at which transcriptional regulators initially bind, leading to subsequent changes in the chromatin at the cognate promoter. Exogenous Myod1 activates its own transcription by binding first at the enhancer leading to an NDR and transcription-permissive chromatin at the associated MYOD1 promoter. Exogenous OCT4 also binds first to the permissive MYOD1 enhancer, but has a different effect on the cognate promoter, where the monovalent H3K27me3-marks are converted to the bivalent state characteristic of stem cells. Genome-wide, a high percentage of Polycomb targets are associated with putative enhancers in permissive states, suggesting they may provide a widespread avenue for the initiation of cell-fate reprogramming.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
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通讯作者：
Jones PA
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64.8
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作者：
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