Howard Hughes Medical Institute and Department of Biochemistry, School of Medicine, New York University, New York, NY 10016, USA.
Science. 2010 Oct 29;330(6004):612-6. doi: 10.1126/science.1191078.
Epigenetic signals are responsible for the establishment, maintenance, and reversal of metastable transcriptional states that are fundamental for the cell's ability to "remember" past events, such as changes in the external environment or developmental cues. Complex epigenetic states are orchestrated by several converging and reinforcing signals, including transcription factors, noncoding RNAs, DNA methylation, and histone modifications. Although all of these pathways modulate transcription from chromatin in vivo, the mechanisms by which epigenetic information is transmitted through cell division remain unclear. Because epigenetic states are metastable and change in response to the appropriate signals, a deeper understanding of their molecular framework will allow us to tackle the dysregulation of epigenetics in disease.
表观遗传信号负责建立、维持和逆转不稳定的转录状态,这些状态是细胞“记住”过去事件(如外部环境变化或发育线索)的能力的基础。几种汇聚和增强的信号,包括转录因子、非编码 RNA、DNA 甲基化和组蛋白修饰,共同调控复杂的表观遗传状态。虽然这些途径都可以调节体内染色质的转录,但表观遗传信息如何通过细胞分裂传递的机制尚不清楚。由于表观遗传状态是不稳定的,并对适当的信号做出反应,因此深入了解它们的分子框架将使我们能够解决疾病中表观遗传失调的问题。