Department of Experimental Oncology, European Institute of Oncology, IFOM-IEO Campus, Via Adamello 16, 20139 Milan, Italy.
Immunity. 2010 Jul 23;33(1):12-24. doi: 10.1016/j.immuni.2010.07.006.
Cell differentiation entails early lineage choices leading to the activation, and the subsequent maintenance, of the gene expression program characteristic of each cell type. Alternative lineage choices involve the activation of different regulatory and coding regions of the genome, a process instructed by lineage-determining transcription factors, and at least in part mediated by the deposition of chromatin marks that modify functionality and accessibility of the underlying genome. According to classic epigenetics, subsequent maintenance of chromatin marks across mitoses and in spite of environmental perturbations occurs largely through autonomous and unsupervised mechanisms. However, paradigmatic genetic and biochemical studies in immune system and hematopoietic cells strongly point to the concept that both induction and maintenance of the differentiated state require constant supervision by lineage-determining transcription factors, which may act to globally organize the genome in both the one- and the three-dimensional space.
细胞分化需要早期的谱系选择，从而激活和随后维持每种细胞类型特有的基因表达程序。替代的谱系选择涉及基因组中不同调节和编码区域的激活，这一过程由谱系决定转录因子指导，并至少部分由染色质标记的沉积介导，这些标记改变了基础基因组的功能和可及性。根据经典的表观遗传学，染色质标记在有丝分裂中的后续维持以及尽管存在环境干扰，主要通过自主和无监督的机制发生。然而，免疫系统和造血细胞中的典范遗传和生化研究强烈指出，分化状态的诱导和维持都需要谱系决定转录因子的持续监督，这些转录因子可能作用于在一维和三维空间中全局组织基因组。
