Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA.
Nat Biotechnol. 2010 Oct;28(10):1079-88. doi: 10.1038/nbt.1684.
Epigenetic modifications constitute a complex regulatory layer on top of the genome sequence. Pluripotent and differentiated cells provide a powerful system for investigating how the epigenetic code influences cellular fate. High-throughput sequencing of these cell types has yielded DNA methylation maps at single-nucleotide resolution and many genome-wide chromatin maps. In parallel to epigenome mapping efforts, remarkable progress has been made in our ability to manipulate cell states; ectopic expression of transcription factors has been shown to override developmentally established epigenetic marks and to enable routine generation of induced pluripotent stem (iPS) cells. Despite these advances, many fundamental questions remain. The roles of epigenetic marks and, in particular, of epigenetic modifiers in development and in disease states are not well understood. Although iPS cells appear molecularly and functionally similar to embryonic stem cells, more genome-wide studies are needed to define the extent and functions of epigenetic remodeling during reprogramming.
表观遗传修饰构成了基因组序列之上的一个复杂调控层。多能性和分化细胞为研究表观遗传密码如何影响细胞命运提供了一个强大的系统。对这些细胞类型进行高通量测序，得到了单核苷酸分辨率的 DNA 甲基化图谱和许多全基因组染色质图谱。与表观基因组图谱绘制工作并行，我们在操纵细胞状态方面取得了显著进展；异位表达转录因子已被证明可以覆盖发育过程中建立的表观遗传标记，并能够常规生成诱导多能干细胞（iPS）。尽管取得了这些进展，但仍有许多基本问题尚未解决。表观遗传标记的作用，特别是表观遗传修饰物在发育和疾病状态中的作用，还没有得到很好的理解。尽管 iPS 细胞在分子和功能上与胚胎干细胞相似，但仍需要更多的全基因组研究来定义重编程过程中表观遗传重塑的程度和功能。
