Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos

Beste Mutlu, Huei Mei Chen, James J. Moresco, Barbara D. Orelo, Bing Yang, John M. Gaspar, Sabine Keppler-Ross, John R. Yates, David H. Hall, Eleanor M. Maine, Susan E. Mango

Research output: Contribution to journalArticlepeer-review

Abstract

Heterochromatin formation during early embryogenesis is timed precisely, but it has been elusive how this process is regulated. Here we report the discovery of a histone methyltransferase complex whose nuclear accumulation determines the onset of heterochromatin formation in C. elegans embryos. We find that the inception of heterochromatin generation coincides with the nuclear accumulation of the methyltransferase MET-2 (SETDB). The absence of MET-2 results in delayed and disturbed heterochromatin formation, whereas accelerated nuclear localization of the methyltransferase leads to precocious heterochromatin. We identify two factors that bind to and function with MET-2: LIN-65, which resembles ATF7IP, localizes MET-2 into nuclear hubs, and ARLE-14, orthologous to ARL14EP, promotes stable association of MET-2 with chromatin. These data reveal that nuclear accumulation of MET-2 in conjunction with LIN-65 and ARLE-14 regulates timing of heterochromatin domains during embryogenesis.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - May 18 2018

Keywords

  • Lung
  • Melanoma
  • PCOS
  • Polycystic ovarian syndrome
  • SETDB1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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