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Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival

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

ORGANISM(S): Mus musculus

PROVIDER: GSE273309 | GEO | 2024/09/27

REPOSITORIES: GEO

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Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival.

Project description:The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGO) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the ovarian reserve. Conditional loss of CHD4 in perinatal mouse oocytes results in acute death of NGOs and depletion of the ovarian reserve. CHD4 establishes closed chromatin at regulatory elements of pro-apoptotic genes to prevent cell death and at specific genes required for meiotic prophase I to facilitate the transition from meiotic prophase I oocytes to meiotic arrested NGOs. In addition, CHD4 establishes closed chromatin at the regulatory elements of pro-apoptotic genes in male germ cells, allowing male germ cell survival. These results demonstrate a role for CHD4 in defining a chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of both female and male germ cells.

| S-EPMC11343143 | biostudies-literature

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance and male germ cell survival.

Project description:The ovarian reserve defines female reproductive lifespan, which in humans spans decades due to the maintenance of meiotic arrest in non-growing oocytes (NGOs) residing in primordial follicles. Unknown is how the chromatin state of NGOs is established to enable long-term maintenance of the ovarian reserve. Here, we show that a chromatin remodeler, CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, establishes chromatin states required for formation and maintenance of the ovarian reserve. Conditional loss of CHD4 in perinatal mouse oocytes results in acute death of NGOs and depletion of the ovarian reserve. CHD4 establishes closed chromatin at regulatory elements of pro-apoptotic genes to prevent cell death and at specific genes required for meiotic prophase I to facilitate the transition from meiotic prophase I oocytes to meiotically-arrested NGOs. In male germ cells, CHD4 establishes closed chromatin at the regulatory elements of pro-apoptotic genes, allowing germ cell survival. These results demonstrate a role for CHD4 in defining a chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of both female and male germ cells.

| S-EPMC11795200 | biostudies-literature

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [ATAC-seq]

Project description:To understand the functional role of CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, in establishing chromatin states in the formation and maintenance of ovarian reserve and the maintenance of female and male germ cells, we eliminated CHD4 function in germ cells using Ddx4-Cre and Gdf9-iCre to generate CHD4 conditional knockout (Chd4 DcKO and GcKO) mice. We discover that CHD4 defines the chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of female and male germ cells. We then performed ATAC-seq in Chd4 Dctrl and Chd4 DcKO non-growing oocytes and undifferentiated spermatogonia.

2024-09-27 | GSE273308 | GEO

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [CUT&Tag]

2024-09-27 | GSE273307 | GEO

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [RNA-seq]

Project description:To understand the functional role of CHD4, a member of the Nucleosome Remodeling and Deacetylase (NuRD) complex, in establishing chromatin states in the formation and maintenance of ovarian reserve and the maintenance of female and male germ cells, we eliminated CHD4 function in germ cells using Ddx4-Cre and Gdf9-iCre to generate CHD4 conditional knockout (Chd4 DcKO and GcKO) mice. We discover that CHD4 defines the chromatin state that ensures germ cell survival, thereby enabling the long-term maintenance of female and male germ cells. We then performed gene expression profiling analysis using data obtained from RNA-seq of Chd4 Dctrl and Chd4 DcKO non-growing oocytes and undifferentiated spermatogonia, and Chd4 Gctrl and Chd4 GcKO non-growing and growing oocytes.

2024-09-27 | GSE273306 | GEO

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival

Project description:Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival

| PRJNA1141395 | ENA

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [RNA-seq]

Project description:Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [RNA-seq]

| PRJNA1141405 | ENA

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [CUT&Tag]

Project description:Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [CUT&Tag]

| PRJNA1141404 | ENA

Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [ATAC-seq]

Project description:Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [ATAC-seq]

| PRJNA1141403 | ENA

Nucleosome-CHD4 chromatin remodeler structure maps human disease mutations.

Project description:Chromatin remodeling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodeling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here, we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodeling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.

| S-EPMC7338049 | biostudies-literature

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