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Activating the genome during development and exit from mitosis

机译：在发育过程中激活基因组并退出有丝分裂

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During mitosis, the genome is silent. When cells exitmitosis and re-enter the cell cycle, how does the transcriptionalprogram of a differentiated cell become reactivatedfaithfully and in a timely manner? We previouslyfound that in undifferentiated progenitor cells in theearly embryo, the competence to activate transcriptionallysilent genes is established by pioneer transcriptionfactors, such as FoxA proteins. Pioneer factors have theability to bind their target DNA sequence in compactedchromatin and allow other factors to bind nearby. Wediscovered that the same pioneer transcription factorsthat function in early liver development remain bound tothe genome during liver cell mitosis, when the genomecompacts, most factors and RNA polymerase areexcluded, and transcription is silent. Specifically, the pioneertranscription factor FoxA1 exhibits virtually completemitotic chromosome binding, whereas other liverfactors bind with a range of efficiencies and binding modalities.The evident hierarchy of specific binding, nonspecificbinding, partial chromatin binding, failure to bindmitotic chromosomes, and mitotic instability reflects thefactors’ developmental roles in gene activation, and suggestthat re-activation of the genome following mitosisinvolves a replay of the network by which the cell typewas established in development.
机译：在有丝分裂期间，基因组是沉默的。当细胞退出有丝分裂并重新进入细胞周期时，分化后的细胞的转录程序如何及时如实地重新激活？我们先前发现，在早期胚胎的未分化祖细胞中，激活转录沉默基因的能力是由先驱转录因子（例如FoxA蛋白）建立的。先锋因子有能力在紧缩染色质中结合其靶DNA序列，并允许附近的其他因子结合。我们发现，在肝细胞有丝分裂期间，当基因组紧凑，大多数因子和RNA聚合酶被排除且转录沉默时，在肝细胞早期分裂中起作用的相同的先锋转录因子仍与基因组结合。具体而言，先锋转录因子FoxA1表现出几乎完全的有丝分裂染色体结合，而其他肝因子则具有一系列效率和结合方式。特异性结合，非特异性结合，部分染色质结合，对有丝分裂染色体的破坏和有丝分裂的不稳定性明显反映了该因子的发育。在有丝分裂中起着重要的作用，并暗示有丝分裂后基因组的重新激活涉及网络的重播，通过该重播可以建立细胞类型。

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