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Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis

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

ORGANISM(S): Mus musculus

PROVIDER: GSE214233 | GEO | 2023/06/14

REPOSITORIES: GEO

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ZMYM2 is essential for methylation of germline genes and active transposons in embryonic development.

Project description:ZMYM2 is a transcriptional repressor whose role in development is largely unexplored. We found that Zmym2-/- mice show embryonic lethality by E10.5. Molecular characterization of Zmym2-/- embryos revealed two distinct defects. First, they fail to undergo DNA methylation and silencing of germline gene promoters, resulting in widespread upregulation of germline genes. Second, they fail to methylate and silence the evolutionarily youngest and most active LINE element subclasses in mice. Zmym2-/- embryos show ubiquitous overexpression of LINE-1 protein as well as aberrant expression of transposon-gene fusion transcripts. ZMYM2 homes to sites of PRC1.6 and TRIM28 complex binding, mediating repression of germline genes and transposons respectively. In the absence of ZMYM2, hypermethylation of histone 3 lysine 4 occurs at target sites, creating a chromatin landscape unfavourable for establishment of DNA methylation. ZMYM2-/- human embryonic stem cells also show aberrant upregulation and demethylation of young LINE elements, indicating a conserved role in repression of active transposons. ZMYM2 is thus an important new factor in DNA methylation patterning in early embryonic development.

| S-EPMC10415128 | biostudies-literature

Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [WGBS-seq]

Project description:ZMYM2 is a transcriptional repressor whose role in development is largely unexplored. We found that Zmym2-/- mice show embryonic lethality by E10.5. Molecular characterization of Zmym2-/- embryos revealed two distinct defects. First, they fail to undergo DNA methylation and silencing of germline gene promoters, resulting in widespread upregulation of germline genes. Second, they fail to methylate and silence the evolutionarily youngest and most active LINE element subclasses in mice. This results in ubiquitous overexpression of LINE1 protein as well as aberrant expression of transposon-gene fusion transcripts. Interaction and colocalization data indicate that ZMYM2 homes to germline genes via binding to the non-canonical polycomb complex PRC1.6 and to transposons via the TRIM28 complex. ZMYM2-/- human embryonic stem cells also show aberrant upregulation and demethylation of young LINE elements, indicating a conserved role in repression of active transposons. ZMYM2 is thus an important new factor in DNA methylation patterning in early embryogenesis.

2023-06-14 | GSE214232 | GEO

Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [ChIP-seq]

Project description:ZMYM2 is a transcriptional repressor whose role in development is largely unexplored. We found that Zmym2-/- mice show embryonic lethality by E10.5. Molecular characterization of Zmym2-/- embryos revealed two distinct defects. First, they fail to undergo DNA methylation and silencing of germline gene promoters, resulting in widespread upregulation of germline genes. Second, they fail to methylate and silence the evolutionarily youngest and most active LINE element subclasses in mice. This results in ubiquitous overexpression of LINE1 protein as well as aberrant expression of transposon-gene fusion transcripts. Interaction and colocalization data indicate that ZMYM2 homes to germline genes via binding to the non-canonical polycomb complex PRC1.6 and to transposons via the TRIM28 complex. ZMYM2-/- human embryonic stem cells also show aberrant upregulation and demethylation of young LINE elements, indicating a conserved role in repression of active transposons. ZMYM2 is thus an important new factor in DNA methylation patterning in early embryogenesis.

2023-06-14 | GSE214197 | GEO

Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [RNA-seq]

Project description:ZMYM2 is a transcriptional repressor whose role in development is largely unexplored. We found that Zmym2-/- mice show embryonic lethality by E10.5. Molecular characterization of Zmym2-/- embryos revealed two distinct defects. First, they fail to undergo DNA methylation and silencing of germline gene promoters, resulting in widespread upregulation of germline genes. Second, they fail to methylate and silence the evolutionarily youngest and most active LINE element subclasses in mice. This results in ubiquitous overexpression of LINE1 protein as well as aberrant expression of transposon-gene fusion transcripts. Interaction and colocalization data indicate that ZMYM2 homes to germline genes via binding to the non-canonical polycomb complex PRC1.6 and to transposons via the TRIM28 complex. ZMYM2-/- human embryonic stem cells also show aberrant upregulation and demethylation of young LINE elements, indicating a conserved role in repression of active transposons. ZMYM2 is thus an important new factor in DNA methylation patterning in early embryogenesis.

2023-06-14 | GSE214161 | GEO

Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis

Project description:Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis

| PRJNA884403 | ENA

Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [RNA-seq]

Project description:Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [RNA-seq]

| PRJNA884277 | ENA

Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [ChIP-seq]

Project description:Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [ChIP-seq]

| PRJNA884350 | ENA

Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [WGBS-seq]

Project description:Zmym2 is essential for methylation of germline genes and active transposons in embryogenesis [WGBS-seq]

| PRJNA884412 | ENA

Maternally inherited piRNAs direct transient heterochromatin formation at active transposons during early Drosophila embryogenesis.

Project description:The PIWI-interacting RNA (piRNA) pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. In Drosophila, piRNAs are intergenerationally inherited through the maternal lineage, and this has demonstrated importance in the specification of piRNA source loci and in silencing of I- and P-elements in the germ cells of daughters. Maternally inherited Piwi protein enters somatic nuclei in early embryos prior to zygotic genome activation and persists therein for roughly half of the time required to complete embryonic development. To investigate the role of the piRNA pathway in the embryonic soma, we created a conditionally unstable Piwi protein. This enabled maternally deposited Piwi to be cleared from newly laid embryos within 30 min and well ahead of the activation of zygotic transcription. Examination of RNA and protein profiles over time, and correlation with patterns of H3K9me3 deposition, suggests a role for maternally deposited Piwi in attenuating zygotic transposon expression in somatic cells of the developing embryo. In particular, robust deposition of piRNAs targeting roo, an element whose expression is mainly restricted to embryonic development, results in the deposition of transient heterochromatic marks at active roo insertions. We hypothesize that roo, an extremely successful mobile element, may have adopted a lifestyle of expression in the embryonic soma to evade silencing in germ cells.

| S-EPMC8352587 | biostudies-literature

The remodeling of bivalent chromatin is essential for mouse peri-implantation embryogenesis.

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-07-23 | GSE274495 | GEO