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Endogenous retroviruses direct the evolution of lineage-specific imprinting

ABSTRACT: Endogenous retroviruses direct the evolution of lineage-specific imprinting

PROVIDER: PRJNA521704 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8556480_1.fastq.gz	Fastqsanger.gz
	SRR8556480_2.fastq.gz	Fastqsanger.gz
	SRR8556481_1.fastq.gz	Fastqsanger.gz
	SRR8556481_2.fastq.gz	Fastqsanger.gz

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Endogenous retroviruses direct the evolution of lineage-specific imprinting

Project description:Imprinted genes are expressed from a single parental allele. In mammals, this unusual mode of transcription generally depends on the epigenetic silencing of the other allele by DNA methylation (DNAme) established in the germline. While many species-specific imprinted orthologues have been documented in eutherians, the molecular mechanisms underlying the evolutionary switch from biallelic to imprinted expression are currently unknown. During mouse oogenesis, gametic differentially methylated regions (gDMRs) acquire DNAme in a process guided by transcription. Here we show that transcription initiating in proximal lineage-specific endogenous retroviruses (ERVs) is likely responsible for DNAme established in oocytes at 4/7 mouse-specific and 22/155 human-specific maternal gDMRs. The latter can be further divided into Catarrhini (old-world monkeys and apes)- or Hominoidea (ape)-specific gDMRs, which are embedded within transcription units initiating in ERVs specific to these primate lineages. Using CRISPR-Cas9 mutagenesis, we deleted the relevant murine-specific ERVs upstream of the maternally methylated genes Impact and Slc38a4. Strikingly, imprinting was lost in the offspring of dams harboring these deletions and biallelic expression was observed, revealing a novel evolutionary mechanism by which maternally silenced genes arise from biallelically expressed progenitors.

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