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Z-DNA is Remodeled by ZBTB43 in Prospermatogonia to Safeguard the Germ Line Genome and Epigenome

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE200729 | GEO | 2022/04/14

REPOSITORIES: GEO

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Z-DNA is Remodeled by ZBTB43 in Prospermatogonia to Safeguard the Germ Line Genome and Epigenome (MIRA-seq)

Project description:Mutagenic purine-pyrimidine repeats can adopt the left-handed Z-DNA conformation. DNA breaks at potential Z-DNA sites can lead to somatic mutations in cancer or to germ line mutations which are transmitted to the next generation. It is not known whether any mechanism exists in the germ line to control Z-DNA structure and DNA breaks at purine-pyrimidine repeats. Here, we provide genetic, epigenomic, and biochemical evidence for the existence of a biological process that erases Z-DNA specifically in germ cells of the mouse male fetus. We show that a previously uncharacterized zinc finger protein, ZBTB43, binds to and removes Z-DNA, preventing the formation of DNA double-strand breaks. By removing Z-DNA, ZBTB43 also promotes de novo DNA methylation at CG-containing purine-pyrimidine repeats in prospermatogonia. Therefore, the genomic and epigenomic integrity of the species is safeguarded by remodeling DNA structure in the mammalian germ line during a critical window of germline epigenome reprogramming.

2022-04-14 | GSE200728 | GEO

Z-DNA is Remodeled by ZBTB43 in Prospermatogonia to Safeguard the Germ Line Genome and Epigenome (ChIP-seq)

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Z-DNA is Remodeled by ZBTB43 in Prospermatogonia to Safeguard the Germ Line Genome and Epigenome (Affinity-seq)

2022-04-14 | GSE200719 | GEO

Z-DNA is remodelled by ZBTB43 in prospermatogonia to safeguard the germline genome and epigenome.

Project description:Mutagenic purine-pyrimidine repeats can adopt the left-handed Z-DNA conformation. DNA breaks at potential Z-DNA sites can lead to somatic mutations in cancer or to germline mutations that are transmitted to the next generation. It is not known whether any mechanism exists in the germ line to control Z-DNA structure and DNA breaks at purine-pyrimidine repeats. Here we provide genetic, epigenomic and biochemical evidence for the existence of a biological process that erases Z-DNA specifically in germ cells of the mouse male foetus. We show that a previously uncharacterized zinc finger protein, ZBTB43, binds to and removes Z-DNA, preventing the formation of DNA double-strand breaks. By removing Z-DNA, ZBTB43 also promotes de novo DNA methylation at CG-containing purine-pyrimidine repeats in prospermatogonia. Therefore, the genomic and epigenomic integrity of the species is safeguarded by remodelling DNA structure in the mammalian germ line during a critical window of germline epigenome reprogramming.

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Z-DNA is Remodeled by ZBTB43 in Prospermatogonia to Safeguard the Germ Line Genome and Epigenome

Project description:Z-DNA is Remodeled by ZBTB43 in Prospermatogonia to Safeguard the Germ Line Genome and Epigenome

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