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

Science Advances
Beste MutluSusan E Mango

Abstract

Heterochromatin formation during early embryogenesis is timed precisely, but how this process is regulated remains elusive. We report the discovery of a histone methyltransferase complex whose nuclear accumulation and activation establish the onset of heterochromatin formation in Caenorhabditis elegans embryos. We find that the inception of heterochromatin generation coincides with the accumulation of the histone H3 lysine 9 (H3K9) methyltransferase MET-2 (SETDB) into nuclear hubs. The absence of MET-2 results in delayed and disturbed heterochromatin formation, whereas accelerated nuclear localization of the methyltransferase leads to precocious H3K9 methylation. We identify two factors that bind to and function with MET-2: LIN-65, which resembles activating transcription factor 7-interacting protein (ATF7IP) and localizes MET-2 into nuclear hubs, and ARLE-14, which is orthologous to adenosine 5'-diphosphate-ribosylation factor-like 14 effector protein (ARL14EP) and 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.

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Citations

Oct 3, 2019·EMBO Reports·Takeshi TsusakaYoichi Shinkai
Feb 1, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Chase C WesleyDaniel L Levy
Jun 4, 2020·Viruses·Kei Fukuda, Yoichi Shinkai
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Feb 10, 2019·The Journal of Cell Biology·Colin E DelaneyJan Padeken
Feb 2, 2021·Endocrinology and Metabolism Clinics of North America·Corrine K Welt
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Abhimanyu DasGuptaArneet L Saltzman
Mar 18, 2021·ELife·Leah Houri-ZeeviOded Rechavi
Dec 19, 2020·Current Opinion in Genetics & Development·Peter Askjaer, Jennifer C Harr
Aug 22, 2021·Science Advances·Jadiel A WassonSusan E Mango

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Datasets Mentioned

BETA
GSE113841

Methods Mentioned

BETA
transmission electron microscopy
immunoprecipitation
proximity ligation assay
ChIP-seq
ChIP
Gene Knockout
PCR
genotyping
electrophoresis
Illumina sequencing

Software Mentioned

Volocity
wigCorrelate
bdgcmp
ClustalX2
mosSCI
Photoshop
PCOILS
HMMER
MACS2
RawConverter

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