Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins

PLoS One. 2009 Jul 9;4(7):e6202. doi: 10.1371/journal.pone.0006202.

Abstract

The cohesin protein complex was first recognized for holding sister chromatids together and ensuring proper chromosome segregation. Cohesin also regulates gene expression, but the mechanisms are unknown. Cohesin associates preferentially with active genes, and is generally absent from regions in which histone H3 is methylated by the Enhancer of zeste [E(z)] Polycomb group silencing protein. Here we show that transcription is hypersensitive to cohesin levels in two exceptional cases where cohesin and the E(z)-mediated histone methylation simultaneously coat the entire Enhancer of split and invected-engrailed gene complexes in cells derived from Drosophila central nervous system. These gene complexes are modestly transcribed, and produce seven of the twelve transcripts that increase the most with cohesin knockdown genome-wide. Cohesin mutations alter eye development in the same manner as increased Enhancer of split activity, suggesting that similar regulation occurs in vivo. We propose that cohesin helps restrain transcription of these gene complexes, and that deregulation of similarly cohesin-hypersensitive genes may underlie developmental deficits in Cornelia de Lange syndrome.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Cell Line
  • Chromatids / physiology*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / physiology*
  • Drosophila / genetics*
  • Drosophila Proteins / genetics*
  • Gene Expression Regulation / physiology*
  • Gene Knockdown Techniques
  • Homeodomain Proteins / genetics*
  • Mutation
  • Phenotype
  • RNA Interference
  • Repressor Proteins / genetics*
  • Transcription Factors / genetics*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Drosophila Proteins
  • E(spl)m7-HLH protein, Drosophila
  • En protein, Drosophila
  • Homeodomain Proteins
  • Repressor Proteins
  • Transcription Factors
  • cohesins
  • inv protein, Drosophila