Chromatin remodeler CHD4 establishes chromatin states required for ovarian reserve formation, maintenance, and germ cell survival [RNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE273306 | GEO | 2024/09/27
REPOSITORIES: GEO
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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
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 CUT&Tag for CHD4 in Chd4 f/f P1 oocytes.
2024-09-27 | GSE273307 | GEO
Project description:Cancer cells undergo major epigenetic alterations and transcriptome changes, including ectopic expression of many tissue- and cell type-specific genes. Here we show that the germline-specific RNA helicase DDX4 forms germ granule-like cytoplasmic ribonucleoprotein (RNP) granules in various human and mouse tumors, but not in cultured cancer cells. The DDX4-compexes in tumors contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptome imbalance and affects the alternative splicing landscape of a large number of genes with reported functions in cancer growth and invasiveness, leading to their compromised capability to form xenograft tumors. Importantly, high expression of DDX4-positive granules is associated with poor survival in patients with squamous cell carcinoma of the head and neck, as well as with the histological grade of prostate cancer. Taken together, these results show that the formation of germ granule-resembling DDX4 granules have prognostic value, and they are involved in transcriptome control in cancer cells to promote malignant properties.
2024-06-10 | PXD044856 | Pride
Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility. Total RNA, including miRNAs, were purified from a total of six individual mouse samples. The tissue collected was obtained from wild-type (control; n=3) and Dicer1 germ cell knockout (mutant; n=3) testes on P18. One miRNA GCKO sample, M36, was determined to be of poor quality and was excluded from the study; thus, a total of five miRNA samples were analyzed.
2012-09-10 | E-GEOD-38895 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility. Total RNA, including miRNAs, were purified from a total of six individual mouse samples. The tissue collected was obtained from wild-type (control; n=3) and Dicer1 germ cell knockout (mutant; n=3) testes on P18.
2012-09-10 | E-GEOD-38891 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility.
2012-09-10 | GSE38895 | GEO
Project description:MicroRNAs (miRNAs) are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNAse III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO) testes by postnatal day 18 (P18). Compared to wild-type (WT) at 8 weeks, GCKO males had no change in body weight, yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed 96% of miRNA genes were down-regulated and 37% of protein-coding genes were differentially expressed in GCKO testes. Interestingly, we observed preferential overexpression of genes on the sex chromosomes in GCKO testes, with more than 80% of the genes overlapping those proposed to undergo meiotic sex chromosome inactivation (MSCI) in the germ cells. Compared to WT, GCKO mice showed higher percentages of cells at early meiotic stages (leptotene and zygotene) but lower percentages at later stages (pachytene, diplotene and metaphase I), providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Furthermore, we observed fewer elongating spermatids with proper translational activation of transition protein 2 (Tnp2), protamine 1 and 2 (Prm1 and Prm2) in GCKO testes after step 12-14. Therefore, deleting Dicer1 in early postnatal germ cells causes misregulation of transcripts encoded by genes on the sex chromosomes, impairs meiotic progression and post-meiotic translational control and results in spermatogenic failure and infertility.
2012-09-10 | GSE38891 | GEO
Project description:Cancer cells undergo major epigenetic alterations and transcriptomic changes, including ectopic expression of many tissue- and cell type-specific genes. Here we show that the germline-specific RNA helicase DDX4 (DEAD-box helicase 4) forms germ granule-like cytoplasmic ribonucleoprotein (RNP) granules in various human tumors, but not in cultured cancer cells. These cancerous DDX4-complexes contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptomic changes and affects the alternative splicing landscape of a large number of genes involved in cancer growth and invasiveness, leading to compromised capability of DDX4-null cancer cells to form xenograft tumors in immunocompromised mice. Importantly, occurrence of DDX4-granules is associated with poor survival in patients with head and neck squamous cell carcinoma, and higher histological grade of prostate cancer. Taken together, these results show that the germ granule-resembling cancerous DDX4-granules control gene expression and promote malignant and invasive properties of cancer cells.
2024-06-13 | GSE262574 | GEO
Project description:We performed mouse single oocyte RNA-seq and bulk oocyte CUT&Tag assays in the current project. In details, SMART-seq based single oocyte RNA-seq was performed at adult GV stage, GV3h stage and MII stage, using control and Dis3 oocyte-speicfic knockout (cKO) oocytes. RiboMinus-seq based single oocyte RNA-seq was performed at adult GV stage using control and Dis3 cKO oocytes, and at p20 GV stage using control, Dis3 cKO, Exosc10 cKO and Dis3/Exosc10 double cKO (dcKO) oocytes. Bulk CUT&Tag of anti-H3K27me3 was done in WT and Dis3 cKO oocytes at adult GV stage, and in WT and Dis3/Exosc10 dcKO oocytes at p20 stage. In addition, CUT&Tag of anti-RNA polymerase II (Ser2+Ser5) was performed in WT and Dis3 cKO oocytes at GV stage. All CUT&Tag experiments share the same rabbit-Igg negative control. All p20 stage oocytes were specified as p20. The non-specified GV oocytes were all adult GV oocytes.
2022-02-11 | GSE196331 | GEO
Project description:Ddx4 (DEAD-box helicase 4) is a well-established marker gene for early-stage germlines and is required for the development of germ cells. Alternative splicing of ddx4 produces a long transcript that is exclusively expressed in zebrafish ovaries. The function of this ovary-specific transcript (ddx4-L) remains unclear. In this study, using the ddx4-L knockout zebrafish model, we found that elimination of ddx4-L results in a decrease in fertilization rate and in the number of mature eggs laid by the female mutants. Transcriptome analysis was performed to identify the underlying changes of gene expression between WT and ddx4-L knockout ovaries. A total of 1134 differentially expressed genes were identified, of which 524 were upregulated and 610 were downregulated. Functional enrichment analysis showed that the terms of negative regulation of fertilization, sperm-egg recognition process, and oocyte meiosis might be affected by elimination of ddx4-L. Furthermore, we found that Sycp1, a synaptonemal complex protein involved in meiosis and fertility, was dramatically decreased in the ddx4-L knockout ovaries at both mRNA and protein levels. Moreover, the activities of transposable elements were analyzed based on the RNA-seq data. The result showed that elimination of ddx4-L causes the derepression of DNA transposons, a subclass of transposable elements, in zebrafish ovaries. In conclusion, the aforementioned findings indicate that the ovary-specific transcript of ddx4 plays an important role in oocyte development and egg quality, possibly by maintaining sycp1 expression and repressing DNA transposons. Our work provide novel insights into the functions and regulatory mechanisms of ddx4 in zebrafish oogenesis.
2024-12-16 | GSE276129 | GEO