Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, 16 Barker Hall, Berkeley, CA 94720-3204, USA.
Curr Opin Genet Dev. 2022 Jun;74:101912. doi: 10.1016/j.gde.2022.101912. Epub 2022 Apr 28.
Abnormalities in chromosome dose can reduce organismal fitness and viability by disrupting the balance of gene expression. Unlike imbalances in chromosome dose that cause pathologies, differences in X-chromosome dose that determine sex are well tolerated. Dosage compensation mechanisms have evolved in diverse species to balance X-chromosome gene expression between sexes. Mechanisms underlying nematode X-chromosome counting to determine sex revealed how small quantitative differences in molecular signals are translated into dramatically different developmental fates. Mechanisms underlying X-chromosome dosage compensation revealed the interplay between chromatin modification and three-dimensional chromosome structure imposed by an X-specific condensin complex to regulate gene expression over vast chromosomal territories. In a surprising twist of evolution, this dosage-compensation condensin complex also regulates lifespan and tolerance to proteotoxic stress.
染色体剂量的异常会通过破坏基因表达的平衡来降低生物体的适应性和生存能力。与导致病变的染色体剂量失衡不同，决定性别X 染色体剂量的差异是可以耐受的。为了在性别之间平衡 X 染色体基因表达，不同物种已经进化出了剂量补偿机制。线虫 X 染色体计数决定性别背后的机制揭示了分子信号的微小定量差异如何转化为截然不同的发育命运。X 染色体剂量补偿的机制揭示了染色质修饰与由 X 特异性凝聚素复合物施加的三维染色体结构之间的相互作用，以调节跨越巨大染色体区域的基因表达。在进化的一个惊人转折中，这种剂量补偿凝聚素复合物也调节寿命和对蛋白毒性应激的耐受性。
