Multiple Histone Methyl-Lysine Readers Ensure Robust Development and Germline Immortality in Caenorhabditis elegans

Genetics. 2018 Nov;210(3):907-923. doi: 10.1534/genetics.118.301518. Epub 2018 Sep 5.

Abstract

Chromatin modifications, including methylation of histone H3 at lysine 27 (H3K27me) by the Polycomb group proteins, play a broadly conserved role in the maintenance of cell fate. Diverse chromatin organization modifier (chromo) domain proteins act as "readers" of histone methylation states. However, understanding the functional relationships among chromo domains and their roles in the inheritance of gene expression patterns remains challenging. Here, we identify two chromo-domain proteins, CEC-1 and CEC-6, as potential readers of H3K27me in Caenorhabditis elegans, where they have divergent expression patterns and contribute to distinct phenotypes. Both cec-1 and cec-6 genetically interact with another chromo-domain gene, cec-3, a reader of H3K9 methylation. Combined loss of cec-1 and cec-3 leads to developmental defects in the adult that result in decreased fitness. Furthermore, loss of cec-6 and cec-3 surprisingly leads to a progressive loss of fertility across generations, a "mortal germline" phenotype. Our results provide evidence of functional compensation between H3K27me and H3K9me heterochromatin pathways, and show that histone methylation readers contribute to both somatic development and transgenerational fitness.

Keywords: C. elegans; CEC; H3K27me3; PRC2; Polycomb proteins; chromodomain proteins; gene silencing; histone methyl-lysine readers; mortal germline; worm.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism
  • Fertility
  • Heterochromatin / metabolism
  • Histones / chemistry*
  • Histones / metabolism*
  • Longevity
  • Lysine / metabolism*
  • Male
  • Methylation
  • Protein Domains
  • Spermatozoa / cytology*
  • Temperature

Substances

  • Caenorhabditis elegans Proteins
  • Heterochromatin
  • Histones
  • Lysine

Associated data

  • figshare/10.6084/m9.figshare.7045148