Allelic histone-to-DNA methylation switch establishes secondary DMR to maintain noncanonical imprinting
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ABSTRACT:
PROVIDER: PRJNA533990 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8936510.fastq.gz | Fastqsanger.gz | |||
| SRR8936520.fastq.gz | Fastqsanger.gz | |||
| SRR8936520_1.fastq.gz | Fastqsanger.gz | |||
| SRR8936520_2.fastq.gz | Fastqsanger.gz | |||
| SRR8936530.fastq.gz | Fastqsanger.gz |
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Project description:Faithful maintenance of genomic imprinting is essential for mammalian development. While germline DNA methylation-dependent (canonical) imprinting is relatively stable during development, the recently discovered oocyte-derived H3K27me3-mediated noncanonical imprinting is mostly transient in early embryos with only a few genes maintain imprinted expression in the extraembryonic lineage. How these few noncanonical imprinted genes maintain their extraembryonic-specific imprinting is unknown. Here we report that maintenance of extraembryonic-specific noncanonical imprinting requires maternal allele-specific de novo DNA methylation (secondary differentially methylation regions; DMRs) at implantation. The secondary DMRs are located at the gene promoters with paternal allele-specific H3K4me3 preformed during preimplantation development. Importantly, genetic ablation of Eed and DNA methyltransferases revealed that both maternal H3K27me3 and zygotic Dnmt3a/3b are required for establishing secondary DMRs and for maintaining noncanonical imprinting. Thus, our study not only reveals the mechanism underlying maintenance of noncanonical imprinting, but also sheds light on how histone modifications in oocytes and preimplantation embryos may shape the secondary DMRs in post-implantation embryos.
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Project description:Genomic imprinting is the parent-of-origin-specific allelic transcriptional silencing observed in mammals, which is governed by DNA methylation established in the gametes and maintained throughout the development. The frequency and extent of epimutations associated with the nine reported imprinting syndromes varies because it is evident that aberrant preimplantation maintenance of imprinted differentially methylated regions (DMRs) may affect multiple loci. Using a custom Illumina GoldenGate array targeting 27 imprinted DMRs, we profiled allelic methylation in 8 imprinting defect patients.
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