Abstract
EHMT2 is the main euchromatic H3K9 methyltransferase. Embryos with zygotic, or maternal mutation in the Ehmt2 gene exhibit variable developmental delay. To understand how EHMT2 prevents variable developmental delay we performed RNA sequencing of mutant and somite stage-matched normal embryos at 8.5–9.5 days of gestation. Using four-way comparisons between delayed and normal embryos we clarified what it takes to be normal and what it takes to develop. We identified differentially expressed genes, for example Hox genes that simply reflected the difference in developmental progression of wild type and the delayed mutant uterus-mate embryos. By comparing wild type and zygotic mutant embryos along the same developmental window we detected a role of EHMT2 in suppressing variation in the transcriptional switches. We identified transcription changes where precise switching during development occurred only in the normal but not in the mutant embryo. At the 6-somite stage, gastrulation-specific genes were not precisely switched off in the Ehmt2−/− zygotic mutant embryos, while genes involved in organ growth, connective tissue development, striated muscle development, muscle differentiation, and cartilage development were not precisely switched on. The Ehmt2mat−/+ maternal mutant embryos displayed high transcriptional variation consistent with their variable survival. Variable derepression of transcripts occurred dominantly in the maternally inherited allele. Transcription was normal in the parental haploinsufficient wild type embryos despite their delay, consistent with their good prospects. Global profiling of transposable elements revealed EHMT2 targeted DNA methylation and suppression at LTR repeats, mostly ERVKs. In Ehmt2−/− embryos, transcription over very long distances initiated from such misregulated ‘driver’ ERVK repeats, encompassing a multitude of misexpressed ‘passenger’ repeats. In summary, EHMT2 reduced transcriptional variation of developmental switch genes and developmentally switching repeat elements at the six-somite stage embryos. These findings establish EHMT2 as a suppressor of transcriptional and developmental variation at the transition between gastrulation and organ specification.
Publisher
Public Library of Science (PLoS)
Subject
Cancer Research,Genetics (clinical),Genetics,Molecular Biology,Ecology, Evolution, Behavior and Systematics
Reference59 articles.
1. Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation;K Ancelin;eLife,2016
2. Histone H3K9 Methyltransferase G9a in Oocytes Is Essential for Preimplantation Development but Dispensable for CG Methylation Protection;WK Au Yeung;Cell Rep,2019
3. Histone Demethylase UTX is an Essential Factor for Zygotic Genome Activation and Regulates Zscan4 Expression in Mouse Embryos;L Bai;International journal of biological sciences,2019
4. Setd1b, encoding a histone 3 lysine 4 methyltransferase, is a maternal effect gene required for the oogenic gene expression program;D Brici;Development,2017
5. KDM1B is a histone H3K4 demethylase required to establish maternal genomic imprints;DN Ciccone;Nature,2009
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