RRC ID 59561
Author Mutlu B, Chen HM, Gutnik S, Hall DH, Keppler-Ross S, Mango SE.
Title Distinct functions and temporal regulation of methylated histone H3 during early embryogenesis.
Journal Development
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.
Volume 146(19)
Published 2019-10-10
DOI 10.1242/dev.174516
PII dev.174516
PMID 31540912
PMC PMC6803369
MeSH Animals Caenorhabditis elegans / embryology* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism Cell Count Embryo, Nonmammalian / cytology Embryonic Development* Gastrulation Heterochromatin / metabolism Histones / metabolism* Interphase Methylation RNA Polymerase II / metabolism S Phase Time Factors Transcription, Genetic
IF 5.763
Times Cited 1
C.elegans tm3713 tm2966 tm892