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 language | English (US) |
|---|---|
| Journal | Development (Cambridge, England) |
| Volume | 146 |
| Issue number | 19 |
| DOIs | |
| State | Published - Oct 10 2019 |
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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 journal › Article
}
TY - JOUR
T1 - Distinct functions and temporal regulation of methylated histone H3 during early embryogenesis
AU - Mutlu, Beste
AU - Chen, Huei Mei
AU - Gutnik, Silvia
AU - Hall, David H.
AU - Keppler-Ross, Sabine
AU - Mango, Susan E.
PY - 2019/10/10
Y1 - 2019/10/10
N2 - 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.
AB - 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.
KW - Embryogenesis
KW - Heterochromatin
KW - met-2
KW - Pluripotency
KW - SETDB1
UR - http://www.scopus.com/inward/record.url?scp=85073126013&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073126013&partnerID=8YFLogxK
U2 - 10.1242/dev.174516
DO - 10.1242/dev.174516
M3 - Article
C2 - 31540912
AN - SCOPUS:85073126013
VL - 146
JO - Development (Cambridge)
JF - Development (Cambridge)
SN - 0950-1991
IS - 19
ER -