TET1-JMJD3-H3K27me3 targets and regulates Pramel3 to affect spermatogonia self-renewal and proliferation and differentiation
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ABSTRACT:
PROVIDER: PRJNA975136 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24686506_1.fastq.gz | Fastqsanger.gz | |||
| SRR24686506_2.fastq.gz | Fastqsanger.gz | |||
| SRR24686507_1.fastq.gz | Fastqsanger.gz | |||
| SRR24686507_2.fastq.gz | Fastqsanger.gz | |||
| SRR24686508_1.fastq.gz | Fastqsanger.gz |
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Project description:Histone modification and DNA methylation among epigenetic modifications play a coordinated role in the regulation of spermatogonia. Tet methylcytosine dioxygenase 1 (TET1) can either act as a DNA demethylase, converting 5-methylcytosine to 5-hydroxymethylcytosine or regulate gene expression by forming a complex with other proteins. Increased levels of H3K27me3 will result in transcriptional repression and reduced or silenced protein expression. However, the mechanism by which TET1 mediates the regulation of H3K27me3 in spermatogonia and the target genes that act is not clear. The results of this study showed that the expression of self-renewal-related gene GFRA1 and proliferation-related gene PCNA were up-regulated after JMJD3 overexpression. Moreover, it was demonstrated that TET1 and JMJD3 can interact with H3K27me3 by forming a protein complex, and the CHIP-Seq sequencing results analyzed that TET1 targets and regulates the Pramel3 gene when interacting with H3K27me3, and TET1 overexpression promotes the up-regulation of Pramel3 expression. Our study identified a novel link between TET1 and H3K27me3 and established a TET1-JMJD3-H3K27me3-Pramel3 regulatory axis to regulate spermatogonia self-renewal, proliferation and differentiation. It provides a new idea to further investigate the mechanism of spermatogenesis and spermatogenic disorders from the epigenetic level.
2023-05-24 | GSE233150 | GEO
Project description:BackgroundIn epigenetic modification, histone modification and DNA methylation coordinate the regulation of spermatogonium. Not only can methylcytosine dioxygenase 1 (TET1) function as a DNA demethylase, converting 5-methylcytosine to 5-hydroxymethylcytosine, it can also form complexes with other proteins to regulate gene expression. H3K27me3, one of the common histone modifications, is involved in the regulation of stem cell maintenance and tumorigenesis by inhibiting gene transcription.Methodswe examined JMJD3 at both mRNA and protein levels and performed Chip-seq sequencing of H3K27me3 in TET1 overexpressing cells to search for target genes and signaling pathways of its action.ResultsThis study has found that JMJD3 plays a leading role in spermatogonia self-renewal and proliferation: at one extreme, the expression of the self-renewal gene GFRA1 and the proliferation-promoting gene PCNA was upregulated following the overexpression of JMJD3 in spermatogonia; at the other end of the spectrum, the expression of differentiation-promoting gene DAZL was down-regulated. Furthermore, the fact that TET1 and JMJD3 can form a protein complex to interact with H3K27me3 has also been fully proven. Then, through analyzing the sequencing results of CHIP-Seq, we found that TET1 targeted Pramel3 when it interacted with H3K27me3. Besides, TET1 overexpression not only reduced H3K27me3 deposition at Pramel3, but promoted its transcriptional activation as well, and the up-regulation of Pramel3 expression was verified in JMJD3-overexpressing spermatogonia.ConclusionIn summary, our study identified a novel link between TET1 and H3K27me3 and established a Tet1-JMJD3-H3K27me3-Pramel3 axis to regulate spermatogonia self-renewal and proliferation. Judging from the evidence offered above, we can safely conclude that this study provides new ideas for further research regarding the mechanism of spermatogenesis and spermatogenesis disorders on an apparent spectrum.
| S-EPMC10905883 | biostudies-literature
Project description:We analyzed 3 repeats of 12 samples of mouse spermatogonia cells including 3-month-old WT and 3 month-old Tet1, 11-month-old WT and 11-month-old Tet1, aimed to find Tet1 function on male fertility.
2020-01-18 | GSE140014 | GEO
Project description:By analyzing the sequencing results of RNA-seq, we found that TET1 maintains self-renewal of mouse spermatogonia and promotes cellular transcription and enhances cellular activity, and we identified key differential genes that are specifically affected by TET1 and the mechanism of interaction between these key differential genes, providing a scientific basis for studying spermatogenesis, revealing the causes of spermatogenic disorders, and elucidated the mechanisms, which may contribute to the understanding of male reproductive disorders.
2022-01-17 | GSE193717 | GEO
Project description:We analysed 2 samples of mouse spermatogonia cells including 3-month-old WT and 3 month-old Tet1
2020-01-18 | GSE140999 | GEO
Project description:Spermatogonia are the source of spermatogenic waves. Abnormal spermatogonia can cause ab-normal spermatogenic waves, which manifest as spermatogenic disorders such as oligospermia, hypospermia, and azoospermia. Among them, the self-renewal of spermatogonia serves as the basis for maintaining the process of spermatogenesis, and the closely regulated balance between self-renewal and differentiation of spermatogonia can maintain the continuous production of spermatozoa. Tet methylcytosine dioxygenase 1(TET1) is an important epitope modifying enzyme that catalyzes the conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), thereby causing the methylation of specific genes site hydroxylation, enabling the DNA de-methylation process, and regulating gene expression. However, the hydroxymethylation sites at which TET1 acts specifically and the mechanisms of interaction affecting key differential genes are not clear. In the present study, we provide evidence that the expression of PLZF, a marker gene for spermatogonia self-renewal, was significantly elevated in the TET1 overexpression group, while the expression of PCNA, a proliferation-related marker gene, was also elevated at the mRNA level. Significant differential expression of SP1 was found by sequencing. SP1 expression was increased at both mRNA level and protein level after TET1 overexpression, while differential gene DAXX expression was downregulated at protein level, while the expression of its reciprocal protein P53 was upregulated. In conclusion, our results suggest that TET1 overexpression causes changes in the expression of SP1, DAXX and other genes, and that there is a certain antagonistic effect between SP1 and DAXX, which eventually reaches a dynamic balance to maintain the self-renewal state of spermatogonia for sustained sperm production. These findings may contribute to the understanding of male reproductive system disorders.
| S-EPMC8879134 | biostudies-literature
Project description:Several signaling pathways require JMJD3 binding to promoters to activate the expression of target genes. Despite the known H3K27me3 demethylase activity of JMJD3 the transcriptional coactivator mechanism remains unclear. Here we reveal that JMJD3 promotes transcription of TGFb responsive genes through regulation of RNAPII progression on gene bodies. ChIPseq experiments demonstrate that upon TGFb treatment, JMJD3 and RNAPII.ser2P colocalyze extensively along intragenic regions of TGF target genes. M-BM- According to these data, genome wide analysis shows that JMJD3 dependent TGF target genes are enriched in H3K27me3 prior to TGF signaling pathway activation. M-BM- Further molecular analysis indicate that JMJD3 removes H3K27me3 and pave the way for the RNAPII.Overall, these findingsM-BM- uncover the mechanism ofM-BM- JMJD3 function in transcriptional activation We performed chromatin immunoprecipitation followed by sequencing (ChIPseq) of H3K27me3 mark in mouse neural stem cells growing under standard conditions. We also performed ChIPseq of elongating RNAPII (Ser2P) and JMJD3 in neural stem cells stimulated with TGFb cytokine.
2012-12-31 | E-GEOD-38269 | biostudies-arrayexpress
Project description:Several signaling pathways require JMJD3 binding to promoters to activate the expression of target genes. Despite the known H3K27me3 demethylase activity of JMJD3 the transcriptional coactivator mechanism remains unclear. Here we reveal that JMJD3 promotes transcription of TGFb responsive genes through regulation of RNAPII progression on gene bodies. ChIPseq experiments demonstrate that upon TGFb treatment, JMJD3 and RNAPII.ser2P colocalyze extensively along intragenic regions of TGF target genes. According to these data, genome wide analysis shows that JMJD3 dependent TGF target genes are enriched in H3K27me3 prior to TGF signaling pathway activation. Further molecular analysis indicate that JMJD3 removes H3K27me3 and pave the way for the RNAPII.Overall, these findings uncover the mechanism of JMJD3 function in transcriptional activation
2012-12-31 | GSE38269 | GEO
Project description:RNA-seq data of Spermatogonia cells of Tet1-ko and WT
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Project description:Sustained spermatogenesis in adult males and recovery of fertility following germ cell depletion are dependent on undifferentiated spermatogonia with self-renewal potential. Self-renewal of undifferentiated spermatogonia is dependent on a complex network of transcriptional and post-transcriptional regulatory factors. DDX5 is known to act as a transcriptional co-regulator in other systems through interactions with key transcription factors. Here, we performed ChIP-Seq to identify target genes of DDX5 in cultured undifferentiated spermatogonia in order to elucidate its role in maintenance of the male germline.
2019-04-02 | GSE110347 | GEO