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Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage

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

ORGANISM(S): Mus musculus

PROVIDER: GSE140621 | GEO | 2020/03/22

REPOSITORIES: GEO

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Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage.

Project description:Zinc finger protein Zscan4 is selectively expressed in mouse two-cell (2C) embryos undergoing zygotic genome activation (ZGA) and in a rare subpopulation of embryonic stem cells with 2C-like features. Here, we show that Zscan4 specifically recognizes a subset of (CA)n microsatellites, repeat sequences prone to genomic instability. Zscan4-associated microsatellite regions are characterized by low nuclease sensitivity and high histone occupancy. In vitro, Zscan4 binds nucleosomes and protects them from disassembly upon torsional strain. Furthermore, Zscan4 depletion leads to elevated DNA damage in 2C mouse embryos in a transcription-dependent manner. Together, our results identify Zscan4 as a DNA sequence-dependent microsatellite binding factor and suggest a developmentally regulated mechanism, which protects fragile genomic regions from DNA damage at a time of embryogenesis associated with high transcriptional burden and genomic stress.

| S-EPMC7083622 | biostudies-literature

Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [ChIP-seq]

Project description:Genome-wide binding analysis of Zscan4 showed sequence-specific occupancy at (CA)n microsatellite repeats in 2C-like cells. Genome-wide occupancy profiling of FACT subunit SSRP1 in curaxin-treated mouse ESC demonstrated re-localization from transcription start sites to Zscan4 binding sites.

2020-03-22 | GSE140619 | GEO

Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [RNA-seq]

Project description:2C-like cells or pluripotent cells were isolated from Zprom::GFP and Zprom::GFP-Zscan4 mouse ESC reporter lines to measure changes in gene expression.

2020-03-22 | GSE140615 | GEO

Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [ATAC-seq]

Project description:ATAC-seq from mouse ESC with stably integrated Zscan4c-GFP reporter.

2020-03-22 | GSE140620 | GEO

Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage

Project description:Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage

| PRJNA590251 | ENA

Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [ATAC-seq]

Project description:Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [ATAC-seq]

| PRJNA590256 | ENA

Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [ChIP-seq]

Project description:Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [ChIP-seq]

| PRJNA590257 | ENA

Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [RNA-seq]

Project description:Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage [RNA-seq]

| PRJNA590258 | ENA

Dnmt1 binds and represses genomic retroelements via DNA methylation in mouse early embryos.

Project description:Genome-wide passive DNA demethylation in cleavage-stage mouse embryos is related to the cytoplasmic localization of the maintenance methyltransferase DNMT1. However, recent studies provided evidences of the nuclear localization of DNMT1 and its contribution to the maintenance of methylation levels of imprinted regions and other genomic loci in early embryos. Using the DNA adenine methylase identification method, we identified Dnmt1-binding regions in four- and eight-cell embryos. The unbiased distribution of Dnmt1 peaks in the genic regions (promoters and CpG islands) as well as the absence of a correlation between the Dnmt1 peaks and the expression levels of the peak-associated genes refutes the active participation of Dnmt1 in the transcriptional regulation of genes in the early developmental period. Instead, Dnmt1 was found to associate with genomic retroelements in a greatly biased fashion, particularly with the LINE1 (long interspersed nuclear elements) and ERVK (endogenous retrovirus type K) sequences. Transcriptomic analysis revealed that the transcripts of the Dnmt1-enriched retroelements were overrepresented in Dnmt1 knockdown embryos. Finally, methyl-CpG-binding domain sequencing proved that the Dnmt1-enriched retroelements, which were densely methylated in wild-type embryos, became demethylated in the Dnmt1-depleted embryos. Our results indicate that Dnmt1 is involved in the repression of retroelements through DNA methylation in early mouse development.

| S-EPMC7470951 | biostudies-literature

Gadusol is a maternally provided sunscreen that protects fish embryos from DNA damage.

Project description:Exposure to ultraviolet radiation (UVR) is harmful to living cells, leading organisms to evolve protective mechanisms against UVR-induced cellular damage and stress.1,2 UVR, particularly UVB (280-320 nm), can damage proteins and DNA, leading to errors during DNA repair and replication. Excessive UVR can induce cellular death. Aquatic organisms face risk of UV exposure as biologically harmful levels of UVB can penetrate >10 m in clear water.3 While melanin is the only known sunscreen in vertebrates, it often emerges late in embryonic development, rendering embryos of many species vulnerable during the earlier stages. Algae and microbes produce a class of sunscreening compounds known as mycosporine-like amino acids (MAAs).4 Fish eggs contain a similar compound called gadusol, whose role as a sunscreen has yet to be tested despite its discovery over 40 years ago.5 The recent finding that many vertebrate genomes contain a biosynthetic pathway for gadusol suggests that many fish may produce and use this molecule as a sunscreen.6 We generated a gadusol-deficient mutant zebrafish to investigate the role of gadusol in protecting fish embryos and larvae from UVR. Our results demonstrate that maternally provided gadusol is the primary sunscreen in embryonic and larval development, while melanin provides modest secondary protection. The gadusol biosynthetic pathway is retained in the vast majority of teleost genomes but is repeatedly lost in species whose young are no longer exposed to UVR. Our data demonstrate that gadusol is a maternally provided sunscreen that is critical for early-life survival in the most species-rich branch of the vertebrate phylogeny.

| S-EPMC10528378 | biostudies-literature

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