Rea S, Akhtar A
Gene expression programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Curr Top Microbiol Immunol. 2006;310:117-40. doi: 10.1007/3-540-31181-5_7.
Epigenetics describes changes in genome function that occur without a change in the DNA sequence. Dosage compensation is a prime example of the regulation of gene expression by an epigenetic mechanism. Dosage compensation has evolved to balance the expression of sex-linked genes in males and females, which possess different numbers of sex chromosomes. However, the genetic sequence of the chromosomes is the same in both sexes. This mechanism therefore needs (1) to function in a sex-specific manner, (2) to target the sex chromosome from amongst the autosomes and (3) to establish and maintain through development a precise, equalised level of gene expression in one sex compared to the other. The process by which dosage compensation is orchestrated has been well characterised in fruit flies and mammals. Although each has evolved a specific dosage-compensation mechanism, these systems share some underlying themes; the molecular components that mediate dosage compensation in both include non-coding RNA molecules, which act as nucleation points for the compensation process. Both systems utilise chromatin-modifying enzymes to remodel large domains of a chromosome. This review will discuss the mechanism of dosage compensation in Drosophila in light of recent developments that have brought into question the previous model of dosage compensation.
表观遗传学描述的是在DNA序列不变的情况下基因组功能发生的变化。剂量补偿是表观遗传机制调控基因表达的一个主要例子。剂量补偿的进化是为了平衡雄性和雌性中与性别相关基因的表达，因为它们拥有不同数量的性染色体。然而，两性染色体的基因序列是相同的。因此，这种机制需要（1）以性别特异性方式发挥作用，（2）从常染色体中靶向性染色体，（3）在发育过程中建立并维持一种性别相对于另一种性别的精确、均衡的基因表达水平。果蝇和哺乳动物中协调剂量补偿的过程已得到充分表征。尽管它们各自进化出了特定的剂量补偿机制，但这些系统有一些共同的基本主题；介导两者剂量补偿的分子成分都包括非编码RNA分子，它们作为补偿过程的成核点。这两个系统都利用染色质修饰酶对染色体的大片段区域进行重塑。鉴于最近的进展对之前的剂量补偿模型提出了质疑，本综述将讨论果蝇中的剂量补偿机制。
