Distinct functions and temporal regulation of methylated histone H3 during early embryogenesis

Beste Mutlu, Huei Mei Chen, Silvia Gutnik, David H. Hall, Sabine Keppler-Ross, Susan E. Mango

Research output: Contribution to journalArticle

Abstract

During the first hours of embryogenesis, formation of higher-order heterochromatin coincides with the loss of developmental potential. Here, we examine the relationship between these two events, and we probe the processes that contribute to the timing of their onset. Mutations that disrupt histone H3 lysine 9 (H3K9) methyltransferases reveal that the methyltransferase MET-2 helps terminate developmental plasticity, through mono- and di-methylation of H3K9 (me1/me2), and promotes heterochromatin formation, through H3K9me3. Although loss of H3K9me3 perturbs formation of higher-order heterochromatin, embryos are still able to terminate plasticity, indicating that the two processes can be uncoupled. Methylated H3K9 appears gradually in developing C. elegans embryos and depends on nuclear localization of MET-2. We find that the timing of H3K9me2 and nuclear MET-2 is sensitive to rapid cell cycles, but not to zygotic genome activation or cell counting. These data reveal distinct roles for different H3K9 methylation states in the generation of heterochromatin and loss of developmental plasticity by MET-2, and identify the cell cycle as a crucial parameter of MET-2 regulation.

Original languageEnglish (US)
JournalDevelopment (Cambridge, England)
Volume146
Issue number19
DOIs
StatePublished - Oct 10 2019

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Heterochromatin
Histones
Embryonic Development
Methylation
Cell Cycle
Embryonic Structures
Methyltransferases
Lysine
Genome
Mutation

Keywords

  • Embryogenesis
  • Heterochromatin
  • met-2
  • Pluripotency
  • SETDB1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Distinct functions and temporal regulation of methylated histone H3 during early embryogenesis. / Mutlu, Beste; Chen, Huei Mei; Gutnik, Silvia; Hall, David H.; Keppler-Ross, Sabine; Mango, Susan E.

In: Development (Cambridge, England), Vol. 146, No. 19, 10.10.2019.

Research output: Contribution to journalArticle

Mutlu, Beste ; Chen, Huei Mei ; Gutnik, Silvia ; Hall, David H. ; Keppler-Ross, Sabine ; Mango, Susan E. / Distinct functions and temporal regulation of methylated histone H3 during early embryogenesis. In: Development (Cambridge, England). 2019 ; Vol. 146, No. 19.
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