Genetic Control of Dosage Compensation

Most animals have two copies of autosomal chromosomes in both females and males. However, females and males have different sex chromosome dosages: males have only one X chromosome instead of two in females. The X chromosome dosage difference must be compensated for the development and survival of animals. This chapter discusses distinct dosage compensationdosage compensation mechanisms in three model systems. Firstly, we will begin with Mary LyonMary Lyon’s hypothesis that one of the two female X chromosomes is inactivated in mammals to equalize the level of X-linked gene expression in both sexes. Identifying the X-inactive-specific transcript (Xist) gene from the X-inactivation center (XIC) has been pivotal for understanding the molecular basis of dosage compensation in mammals. Secondly, we will examine an opposite mechanism in Drosophila, where males’ X chromosome is hyperactivated to compensate for the X dosage difference. Isolation of sex-specific lethal mutations such as male-specific lethal (msl) and maleless (mle) has provided crucial clues to the mechanism of dosage compensation. The roles of the Msl protein complexMsl protein complex and non-coding RNA genes involved in X chromosome-specific gene regulation will be discussed. We will explore another dosage compensation strategy in C. elegans where both female X chromosomes are partially inactivated. We will discuss the similarities and differences of these compensation mechanisms concerning the global regulation of X chromosome gene expression.