体内多梳蛋白动力学和有丝分裂染色质结合将干细胞与分化细胞区分开来。
In vivo Polycomb kinetics and mitotic chromatin binding distinguish stem cells from differentiated cells.
机构信息
Institute of Molecular Biotechnology, Vienna, Austria.
出版信息
Genes Dev. 2012 Apr 15;26(8):857-71. doi: 10.1101/gad.184648.111.
Abstract
Epigenetic memory mediated by Polycomb group (PcG) proteins must be maintained during cell division, but must also be flexible to allow cell fate transitions. Here we quantify dynamic chromatin-binding properties of PH::GFP and PC::GFP in living Drosophila in two cell types that undergo defined differentiation and mitosis events. Quantitative fluorescence recovery after photobleaching (FRAP) analysis demonstrates that PcG binding has a higher plasticity in stem cells than in more determined cells and identifies a fraction of PcG proteins that binds mitotic chromatin with up to 300-fold longer residence times than in interphase. Mathematical modeling examines which parameters best distinguish stem cells from differentiated cells. We identify phosphorylation of histone H3 at Ser 28 as a potential mechanism governing the extent and rate of mitotic PC dissociation in different lineages. We propose that regulation of the kinetic properties of PcG-chromatin binding is an essential factor in the choice between stability and flexibility in the establishment of cell identities.
摘要
表观遗传记忆由多梳组（PcG）蛋白介导，在细胞分裂过程中必须维持，但也必须具有灵活性，以允许细胞命运转变。在这里，我们在两种经历明确分化和有丝分裂事件的细胞类型中，定量研究了活体果蝇中 PH::GFP 和 PC::GFP 的动态染色质结合特性。定量光漂白后荧光恢复（FRAP）分析表明，PcG 结合在干细胞中的可塑性高于更确定的细胞，并且鉴定出一部分 PcG 蛋白与有丝分裂染色质结合的停留时间长达 300 倍以上，而在有丝分裂前期则较短。数学模型检查了哪些参数可以最好地区分干细胞和分化细胞。我们确定组蛋白 H3 在丝氨酸 28 处的磷酸化是控制不同谱系中 PcG 解离的程度和速度的潜在机制。我们提出，PcG-染色质结合动力学特性的调节是在建立细胞身份的稳定性和灵活性之间做出选择的一个重要因素。
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本文引用的文献
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