Benayahu Dafna, Shefer Gabi, Shur Irena
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Front Biosci (Landmark Ed). 2009 Jan 1;14(2):398-409. doi: 10.2741/3251.
Acquisition of lineage specific fate depends on the well orchestrated performance of master transcription factors and on dynamic changes in chromatin structure that account for epigenetic regulation. Epigenetic mechanisms regulate transcription at the promoter level and involve the recruitment of numerous chromatin modifiers in order to permit tissue-selective gene transcription. The dynamics of chromatin structural changes are achieved by the actions of two classes of enzymes: ATP-dependent chromatin remodelers, and histone modifying enzymes. The enzymes are partners in multi-protein complexes that activate or repress transcription depending on the composition of the protein complex. It is fully appreciated now that mechanisms triggering changes in chromatin structure are an integral in determining the stem cell fate. Elucidating the nature of cross talk between chromatin remodelers and master genes is important for identifying pathways that govern stem cell fate and lineage decision.
细胞谱系特异性命运的获得取决于主转录因子精心编排的作用以及染色质结构的动态变化,这些变化构成了表观遗传调控。表观遗传机制在启动子水平调节转录,并涉及招募众多染色质修饰因子以实现组织选择性基因转录。染色质结构变化的动态过程是由两类酶的作用实现的:ATP依赖的染色质重塑酶和组蛋白修饰酶。这些酶是多蛋白复合物中的伙伴,根据蛋白质复合物的组成激活或抑制转录。现在人们充分认识到,触发染色质结构变化的机制是决定干细胞命运不可或缺的一部分。阐明染色质重塑酶与主基因之间的相互作用本质,对于识别控制干细胞命运和谱系决定的途径至关重要。