X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila

Nature. 2011 Mar 3;471(7336):115-8. doi: 10.1038/nature09757.

Abstract

The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Cell Line
  • Chromosomes, Insect / genetics*
  • Chromosomes, Insect / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dosage Compensation, Genetic / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics*
  • Genes, Insect / genetics
  • Genes, X-Linked / genetics
  • Histones / chemistry
  • Histones / metabolism
  • Male
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA Polymerase II / metabolism
  • Sequence Analysis, DNA
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic* / genetics
  • X Chromosome / genetics*
  • X Chromosome / metabolism

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Histones
  • Nuclear Proteins
  • Transcription Factors
  • msl-2 protein, Drosophila
  • RNA Polymerase II

Associated data

  • GEO/GSE25321
  • GEO/GSE25887