New Partners in Regulation of Gene Expression: The Enhancer of Trithorax and Polycomb Corto Interacts With Methylated Ribosomal Protein l12 via Its Chromodomain

PLoS Genet. 2012;8(10):e1003006. doi: 10.1371/journal.pgen.1003006. Epub 2012 Oct 11.

Abstract

Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA-seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism*
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Genome-Wide Association Study
  • HSP70 Heat-Shock Proteins / genetics
  • Lysine / metabolism
  • Methylation
  • Molecular Sequence Data
  • Phenotype
  • Polycomb Repressive Complex 1 / metabolism*
  • Polytene Chromosomes / genetics
  • Polytene Chromosomes / metabolism
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Sequence Alignment
  • Transcription, Genetic
  • Transcriptome

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Drosophila Proteins
  • HSP70 Heat-Shock Proteins
  • Pc protein, Drosophila
  • Ribosomal Proteins
  • corto protein, Drosophila
  • trx protein, Drosophila
  • Polycomb Repressive Complex 1
  • Lysine

Grant support

This work was supported by CNRS and UPMC, PEPS (CNRS) to SB, and “Appel à projets” (IFR 83) to FP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.