Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Stem Cells. 2012 Sep;30(9):1793-9. doi: 10.1002/stem.1169.
The ability to reprogram somatic cells to pluripotency is continuingly attracting increasing amounts of attention, providing both potential opportunities for regenerative medicine, as well as an intriguing model to study basic mechanisms of developmental reversal and epigenetic erasure. Currently, nuclear reprogramming is an inefficient process and a better understanding of its components and the underlying mechanisms will no doubt enable us to increase its robustness and to gain a deeper understanding of its regulation. Here we focus on the reprogramming process from the chromatin and genome organization perspective, describing the chromatin changes that occur both globally and locally. At the global level, chromatin decondenses toward the characteristic 'open' state, while locally, chromatin reorganization supports the silencing of lineage-specific genes and the activation of pluripotency-related genes. Importantly, the proteins that regulate this process are being identified, revealing different layers of chromatin regulation, including histone modifications, histone variants, chromatin remodeling and genomic DNA methylation. The emerging theme is that chromatin and genome organization are not only altered during the transition from a somatic to a pluripotent state, but also play active, regulatory roles during the reprogramming process.
体细胞重编程为多能性的能力不断引起越来越多的关注,为再生医学提供了潜在的机会,同时也为研究发育逆转和表观遗传擦除的基本机制提供了一个有趣的模型。目前,核重编程是一个低效的过程,更好地了解其组成部分和潜在机制无疑将使我们能够提高其稳健性,并更深入地了解其调控机制。在这里,我们从染色质和基因组组织的角度关注重编程过程,描述全局和局部发生的染色质变化。在全局水平上,染色质解凝聚到特征性的“开放”状态,而在局部,染色质重组织支持谱系特异性基因的沉默和多能性相关基因的激活。重要的是,调节这个过程的蛋白质正在被鉴定出来,揭示了不同层次的染色质调控,包括组蛋白修饰、组蛋白变体、染色质重塑和基因组 DNA 甲基化。出现的主题是,在从体细胞到多能性状态的转变过程中,染色质和基因组组织不仅发生改变,而且在重编程过程中也发挥着积极的调节作用。