Dosage compensation in Drosophila melanogaster: epigenetic fine-tuning of chromosome-wide transcription

Many organisms have evolved dosage compensation mechanisms to normalize gene expression levels when copy numbers of sex chromosomes and autosomes are unequal. This Review discusses how multiple epigenetic processes fine-tune the twofold upregulation of gene expression across the entire male X chromosome ofDrosophila melanogaster. Dosage compensation is an epigenetic mechanism that normalizes gene expression from unequal copy numbers of sex chromosomes. Different organisms have evolved alternative molecular solutions to this task. In Drosophila melanogaster, transcription of the single male X chromosome is upregulated by twofold in a process orchestrated by the dosage compensation complex. Despite this conceptual simplicity, dosage compensation involves multiple coordinated steps to recognize and activate the entire X chromosome. We are only beginning to understand the intriguing interplay between multiple levels of local and long-range chromatin regulation required for the fine-tuned transcriptional activation of a heterogeneous gene population. This Review highlights the known facts and open questions of dosage compensation in D. melanogaster.