Genetics Program, Michigan State University , East Lansing, MI, USA.
Genetics Program, Michigan State University , East Lansing, MI, USA ; Department of Biochemistry and Molecular Biology, Michigan State University , East Lansing, MI, USA.
Front Genet. 2015 Feb 10;6:29. doi: 10.3389/fgene.2015.00029. eCollection 2015.
Temporal and spatial control of transcription in development is dictated to a great extent by transcriptional repressors. Some repressor complexes, such as Polycomp-group proteins, induce relatively long-term non-permissive states, whereas others such as hairy/enhancer of split (HES) family repressors are linked to dynamically modulated chromatin states associated with cycling expression of target genes. The mode of action and specificity of repressors involved in mediating this latter form of epigenetic control are unknown. Oscillating expression of HES repressors controlled by signaling pathways such as Notch suggests that the entire ensemble of HES-associated co-repressors and histone modifying complexes readily cycle on and off genes. Dynamic interactions between these factors and chromatin seem to be crucial in maintaining multipotency of progenitor cells, but the significance of such interactions in more differentiated cells is less well understood. We discuss here how genome-wide analyses and real-time gene expression measurements of HES regulated genes can help decipher the detailed mechanisms and biological importance of highly dynamic transcriptional switching mediated by epigenetic changes.
转录在很大程度上受到转录抑制剂的时空控制。一些抑制剂复合物，如 Polycomp 组蛋白，诱导相对长期的非许可状态，而其他如 hairy/enhancer of split (HES) 家族抑制剂与与靶基因表达循环相关的动态调节染色质状态有关。参与介导这种表观遗传控制形式的抑制剂的作用模式和特异性尚不清楚。由 Notch 等信号通路控制的 HES 抑制剂的振荡表达表明，整个 HES 相关共抑制剂和组蛋白修饰复合物很容易在基因上循环开启和关闭。这些因素与染色质之间的动态相互作用似乎对维持祖细胞的多能性至关重要，但这种相互作用在更分化的细胞中的意义还不太清楚。我们在这里讨论了如何通过全基因组分析和实时测量 HES 调节基因的表达来帮助破译由表观遗传变化介导的高度动态转录开关的详细机制和生物学重要性。
