Two C. elegans histone methyltransferases repress lin-3 EGF transcription to inhibit vulval development

Erik C. Andersen, H. Robert Horvitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Studies of Schizosaccharomyces pombe and mammalian cells identified a series of histone modifications that result in transcriptional repression. Lysine 9 of histone H3 (H3K9) is cleacetylated by the NuRD complex, methylated by a histone methyltransferase (HMT) and then bound by a chromodomain-containing protein, such as heterochromatin protein 1 (HP1), leading to transcriptional repression. A Caenorhabditis elegans NuRD-like complex and HP1 homologs regulate vulval development, but no HMT is known to act in this process. We surveyed all 38 putative HMT genes in C. elegans and identified met-1 and met-2 as negative regulators of vulval cell-fate specification. met-1 is homologous to Saccharomyces cerevisiae Set2, an H3K36 HMT that prevents the ectopic initiation of transcription. met-2 is homologous to human SETDB1, an H3K9 HMT that represses transcription. met-1 and met-2 (1) are each required for the normal trimethylation of both H3K9 and H3K36; (2) act redundantly with each other as well as with the C. elegans HP1 homologs; and (3) repress transcription of the EGF gene lin-3, which encodesthe signal that induces vulval development. We propose that as is the case for Set2 in yeast, MET-1 prevents the reinitiation of transcription. Our results suggest that in the inhibition of vulval cleve opment, homologs of SETDB1, HP1 and the NuRD complex act with this H3K36 HMT to prevent ectopic transcriptional initiation.

Original languageEnglish (US)
Pages (from-to)2991-2999
Number of pages9
JournalDevelopment
Volume134
Issue number16
DOIs
StatePublished - Aug 2007

Keywords

  • C. elegens
  • Histone methytransferase
  • SETDB1
  • Set2

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Two C. elegans histone methyltransferases repress lin-3 EGF transcription to inhibit vulval development'. Together they form a unique fingerprint.

Cite this