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Brief Funct Genomics. 2013 Nov;12(6):512-24. doi: 10.1093/bfgp/elt027. Epub 2013 Aug 6.
Three interlocking problems in gene regulation are: how to explain genome-wide targeting of transcription factors in different cell types, how prior transcription factor action can establish an 'epigenetic state' that changes the options for future transcription factor action, and how directly a sequence of developmental decisions can be memorialized in a hierarchy of repression structures applied to key genes of the 'paths not taken'. This review uses the finely staged process of T-cell lineage commitment as a test case in which to examine how changes in developmental status are reflected in changes in transcription factor expression, transcription factor binding distribution across genomic sites, and chromatin modification. These are evaluated in a framework of reciprocal effects of previous chromatin structure features on transcription factor access and of transcription factor binding on other factors and on future chromatin structure.
如何解释转录因子在不同细胞类型中的全基因组靶向；先前的转录因子作用如何建立一种“表观遗传状态”，改变未来转录因子作用的选择；以及发育决策的序列如何直接以应用于“未选择路径”的关键基因的抑制结构层次的方式被记忆。本综述以 T 细胞谱系分化的精细分期过程作为一个测试案例，来研究发育状态的变化如何反映在转录因子表达、转录因子结合在基因组位点上的分布以及染色质修饰的变化中。这些都在先前染色质结构特征对转录因子的可及性以及转录因子结合对其他因子和未来染色质结构的影响的相互作用的框架内进行评估。
