Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Semin Cell Dev Biol. 2017 Dec;72:77-86. doi: 10.1016/j.semcdb.2017.10.022. Epub 2017 Oct 28.
The commitment to and execution of differentiation programmes involves a significant change in gene expression in the precursor cell to facilitate development of the mature cell type. In addition to being regulated by lineage-determining and auxiliary transcription factors that drive these changes, the structural status of the chromatin has a considerable impact on the transcriptional competence of differentiation-specific genes, which is clearly demonstrated by the large number of cofactors and the extraordinary complex mechanisms by which these genes become activated. The terminal differentiation of myoblasts to myotubes and mature skeletal muscle is an excellent system to illustrate these points. The MyoD family of closely related, lineage-determining transcription factors directs, largely through targeting to chromatin, a cascade of cooperating transcription factors and enzymes that incorporate or remove variant histones, post-translationally modify histones, and alter nucleosome structure and positioning via energy released by ATP hydrolysis. The coordinated action of these transcription factors and enzymes prevents expression of differentiation-specific genes in myoblasts and facilitates the transition of these genes from transcriptionally repressed to activated during the differentiation process. Regulation is achieved in both a temporal as well as spatial manner, as at least some of these factors and enzymes affect local chromatin structure at myogenic gene regulatory sequences as well as higher-order genome organization. Here we discuss the transition of genes that promote myoblast differentiation from the silenced to the activated state with an emphasis on the changes that occur to individual histones and the chromatin structure present at these loci.
分化方案的承诺和执行涉及前体细胞中基因表达的显著变化，以促进成熟细胞类型的发育。除了受谱系决定和辅助转录因子的调节外，染色质的结构状态对分化特异性基因的转录能力有很大的影响，这可以通过大量的辅助因子和这些基因被激活的非凡复杂机制得到明显证明。成肌细胞向肌管和成熟骨骼肌的终末分化是一个很好的系统来阐明这些观点。MyoD 家族是密切相关的谱系决定转录因子，主要通过靶向染色质，引导一系列协同作用的转录因子和酶，这些转录因子和酶掺入或去除变体组蛋白，对组蛋白进行翻译后修饰，并通过 ATP 水解释放的能量改变核小体结构和定位。这些转录因子和酶的协调作用防止了成肌细胞中分化特异性基因的表达，并促进了这些基因在分化过程中从转录抑制状态向激活状态的转变。调节是通过时间和空间的方式实现的，因为至少一些这些因素和酶会影响肌生成基因调控序列以及更高阶基因组组织的局部染色质结构。在这里，我们讨论了促进成肌细胞分化的基因从沉默状态到激活状态的转变，重点是发生在单个组蛋白上的变化以及这些基因座上存在的染色质结构。
