1] Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center. [2] Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, 1808 Park Road 1C, Smithville, Texas 78957, USA. [3] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, USA.
Nat Rev Genet. 2014 Feb;15(2):93-106. doi: 10.1038/nrg3607. Epub 2013 Dec 24.
Cellular differentiation is, by definition, epigenetic. Genome-wide profiling of pluripotent cells and differentiated cells suggests global chromatin remodelling during differentiation, which results in a progressive transition from a fairly open chromatin configuration to a more compact state. Genetic studies in mouse models show major roles for a variety of histone modifiers and chromatin remodellers in key developmental transitions, such as the segregation of embryonic and extra-embryonic lineages in blastocyst stage embryos, the formation of the three germ layers during gastrulation and the differentiation of adult stem cells. Furthermore, rather than merely stabilizing the gene expression changes that are driven by developmental transcription factors, there is emerging evidence that chromatin regulators have multifaceted roles in cell fate decisions.
细胞分化从定义上讲是表观遗传的。对多能细胞和分化细胞的全基因组分析表明，在分化过程中存在广泛的染色质重塑，导致染色质从相当开放的构象逐渐转变为更紧凑的状态。在小鼠模型中的遗传研究表明，各种组蛋白修饰酶和染色质重塑因子在关键的发育转变中发挥主要作用，例如囊胚期胚胎中胚胎和胚外谱系的分离、原肠胚形成过程中三个胚层的形成以及成体干细胞的分化。此外，染色质调控因子在细胞命运决定中具有多方面的作用，而不仅仅是稳定发育转录因子驱动的基因表达变化。
