Blum Roy
Biomol Concepts. 2015 Apr;6(2):119-36. doi: 10.1515/bmc-2015-0008.
The ability to regulate gene expression in response to environmental alterations is vital for the endurance of all cells. However, unlike bacteria and unicellular organisms, cells of multicellular eukaryotes have developed this competency in a highly sophisticated manner, which ultimately allows for multiple lineages of differentiated cells. To maintain stability and generate progeny, differentiated cells must remain lineage-committed through numerous cell generations, and therefore their transcriptional modus operandi ought to be memorized and transmittable. To preserve the specialized characteristics of differentiated cells, it is crucial that transcriptional alterations that are triggered by specific external or intrinsic stimuli can last also after stimuli fading and propagate onto daughter cells. The unique composition of DNA and histones, and their ability to acquire a variety of epigenetic modifications, enables eukaryotic chromatin to assimilate cellular plasticity and molecular memory. The most well-studied types of epigenetic modifiers are covalently modifying DNA or histones, mostly in a reversible manner. Additional epigenetic mechanisms include histone variant replacement, energy-utilizing remodeling factors, and noncoding transcripts assembled with modifying complexes. Working with multifunctional complexes including transcription factors, epigenetic modifiers have the potential to dictate a variety of transcriptional programs underlying all cellular lineages, while utilizing in each the same source DNA as their substrates.
响应环境变化调节基因表达的能力对所有细胞的存活至关重要。然而，与细菌和单细胞生物不同，多细胞真核生物的细胞以高度复杂的方式发展了这种能力，这最终产生了多种分化细胞谱系。为了维持稳定性并产生后代，分化细胞必须在众多细胞世代中保持谱系承诺，因此它们的转录操作方式应该被记住并可传递。为了保持分化细胞的特殊特征，至关重要的是，由特定外部或内在刺激引发的转录改变在刺激消失后也能持续，并传递给子细胞。DNA和组蛋白的独特组成及其获得各种表观遗传修饰的能力，使真核染色质能够吸收细胞可塑性和分子记忆。研究最深入的表观遗传修饰类型是以共价方式修饰DNA或组蛋白，大多是可逆的。其他表观遗传机制包括组蛋白变体替换、利用能量的重塑因子以及与修饰复合物组装在一起的非编码转录本。表观遗传修饰因子与包括转录因子在内的多功能复合物协同工作，有可能决定所有细胞谱系潜在的各种转录程序，同时在每个细胞中利用相同的源DNA作为它们的底物。
