Transcriptional repression of Hox genes by C. elegans HP1/HPL and H1/HIS-24

PLoS Genet. 2012 Sep;8(9):e1002940. doi: 10.1371/journal.pgen.1002940. Epub 2012 Sep 13.

Abstract

Elucidation of the biological role of linker histone (H1) and heterochromatin protein 1 (HP1) in mammals has been difficult owing to the existence of a least 11 distinct H1 and three HP1 subtypes in mice. Caenorhabditis elegans possesses two HP1 homologues (HPL-1 and HPL-2) and eight H1 variants. Remarkably, one of eight H1 variants, HIS-24, is important for C. elegans development. Therefore we decided to analyse in parallel the transcriptional profiles of HIS-24, HPL-1/-2 deficient animals, and their phenotype, since hpl-1, hpl-2, and his-24 deficient nematodes are viable. Global transcriptional analysis of the double and triple mutants revealed that HPL proteins and HIS-24 play gene-specific roles, rather than a general repressive function. We showed that HIS-24 acts synergistically with HPL to allow normal reproduction, somatic gonad development, and vulval cell fate decision. Furthermore, the hpl-2; his-24 double mutant animals displayed abnormal development of the male tail and ectopic expression of C. elegans HOM-C/Hox genes (egl-5 and mab-5), which are involved in the developmental patterning of male mating structures. We found that HPL-2 and the methylated form of HIS-24 specifically interact with the histone H3 K27 region in the trimethylated state, and HIS-24 associates with the egl-5 and mab-5 genes. Our results establish the interplay between HPL-1/-2 and HIS-24 proteins in the regulation of positional identity in C. elegans males.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Chromosomal Proteins, Non-Histone* / deficiency
  • Chromosomal Proteins, Non-Histone* / genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / deficiency
  • Histones / genetics*
  • Histones / metabolism
  • Homeodomain Proteins / metabolism
  • Male
  • Methylation
  • Mutation
  • Tail / growth & development
  • Transcription Factors / metabolism
  • Vulva / cytology
  • Vulva / growth & development

Substances

  • Caenorhabditis elegans Proteins
  • Chromosomal Proteins, Non-Histone
  • Egl-5 protein, C elegans
  • HPL-1 protein, C elegans
  • HPL-2 protein, C elegans
  • Histones
  • Homeodomain Proteins
  • Mab-5 protein, C elegans
  • Mes-1 protein, C elegans
  • Transcription Factors
  • Histone-Lysine N-Methyltransferase

Associated data

  • GEO/GSE33339

Grants and funding

This work was supported by the German National Funding Agency (DFG: JE 505/1-3 to MJ-B) and the Max Planck Society (MJ-B). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.