Dosage Compensation in Drosophila—a Model for the Coordinate Regulation of Transcription

Abstract

The sex chromosomes have special significance in the history of genetics. The chromosomal basis of inheritance was firmly established when Calvin Bridges demonstrated that exceptions to Mendel's laws of segregation were accompanied at the cytological level by exceptional sex chromosome segregation. The morphological differences between X and Y exploited in Bridges' experiments arose as a consequence of the evolution of the sex chromosomes. Originally a homologous chromosome pair, the degeneration of the Y chromosome has been accompanied by a requirement for increased expression of the single X chromosome in males. Drosophila has been a model for the study of this dosage compensation and has brought key strengths, including classical genetics, the exceptional cytology of polytene chromosomes, and more recently, comprehensive genomics. The impact of these studies goes beyond sex chromosome regulation, providing valuable insights into mechanisms for the establishment and maintenance of chromatin domains, and for the coordinate regulation of transcription.

Dynamic Sex Chromosome Expression in Drosophila Male Germ Cells

“…Expression of the single X chromosome relative to the major autosomes (chromosomes 2 and 3, each present in two copies) is not significantly different in spermatogonia or any of the somatic cell types using either all expressed genes or widely expressed genes (Fig 3A, B). The somatic cell expression pattern is consistent with the known canonical X chromosome dosage compensation mechanism in somatic cells (21). Our data provides new evidence for noncanonical dosage compensation of the X chromosome in spermatogonia.…”

“…In Drosophila somatic cells, this X chromosome dosage compensation is also essential and involves large-scale transcriptional up-regulation of the single X chromosome (21). It is unclear if dosage compensation exists in Drosophila germ cells, which do not require the core dosage compensation machinery (22,23) suggesting that either dosage compensation does not occur, or if it does, that it relies on a novel mechanism.…”

Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement

“…According to the prevalent model, targeting the X‐chromosome for dosage compensation in Drosophila requires at least two distinct steps: first, the DCC must associate with genetically encoded high‐affinity DNA binding sites. Second, the complex must spread to epigenetically marked active transcription units to disseminate the activating H4 acetylation . We and others suggested that this dissemination may involve dynamic interactions between chromosomal regions of primary binding and target genes in the active nuclear compartment .…”

Dynamic Control of X Chromosome Conformation and Repression by a Histone H4K20 Demethylase

“…imprinted gene clusters, hox clusters) (Andrey et al, 2013; Plasschaert and Bartolomei, 2014; Williamson et al, 2012), or across entire chromosomes (e.g. X-chromosome dosage compensation) (da Rocha and Heard, 2017; Kuroda et al, 2016; Meyer, 2010; Strome et al, 2014). Post-translational modifications of histones and three-dimensional chromosome architecture are prime elements of long-range gene regulation, but their functional interplay in controlling gene expression has been elusive (Dekker and Mirny, 2016; Soshnev et al, 2016).…”