Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg im Breisgau, Germany; email:
Faculty of Biology, University of Freiburg, 79104 Freiburg im Breisgau, Germany.
Annu Rev Biochem. 2018 Jun 20;87:323-350. doi: 10.1146/annurev-biochem-062917-011816. Epub 2018 Apr 18.
X chromosome regulation represents a prime example of an epigenetic phenomenon where coordinated regulation of a whole chromosome is required. In flies, this is achieved by transcriptional upregulation of X chromosomal genes in males to equalize the gene dosage differences in females. Chromatin-bound proteins and long noncoding RNAs (lncRNAs) constituting a ribonucleoprotein complex known as the male-specific lethal (MSL) complex or the dosage compensation complex mediate this process. MSL complex members decorate the male X chromosome, and their absence leads to male lethality. The male X chromosome is also enriched with histone H4 lysine 16 acetylation (H4K16ac), indicating that the chromatin compaction status of the X chromosome also plays an important role in transcriptional activation. How the X chromosome is specifically targeted and how dosage compensation is mechanistically achieved are central questions for the field. Here, we review recent advances, which reveal a complex interplay among lncRNAs, the chromatin landscape, transcription, and chromosome conformation that fine-tune X chromosome gene expression.
X 染色体调控是表观遗传现象的一个主要范例，需要协调整个染色体的调控。在果蝇中，雄性通过转录上调 X 染色体基因来实现这一点，从而使雌性的基因剂量差异达到平衡。构成核糖核蛋白复合物（称为雄性特异性致死（MSL）复合物或剂量补偿复合物）的染色质结合蛋白和长非编码 RNA（lncRNA）介导了这一过程。MSL 复合物成员修饰雄性 X 染色体，如果缺失则会导致雄性致死。雄性 X 染色体还富含组蛋白 H4 赖氨酸 16 乙酰化（H4K16ac），这表明 X 染色体的染色质紧缩状态也在转录激活中发挥重要作用。X 染色体如何被特异性靶向以及如何在机制上实现剂量补偿是该领域的核心问题。在这里，我们回顾了最近的进展，这些进展揭示了 lncRNA、染色质景观、转录和染色体构象之间的复杂相互作用，这些相互作用可以精细调节 X 染色体基因的表达。
