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The arginine methyltransferase CARM1 represses p300•ACT•CREMt axis and is required for spermiogenesis

ABSTRACT: DEGs in the round and elongating spermatids between the WT and Carm1-null testis.

ORGANISM(S): Mus musculus

PROVIDER: GSE107984 | GEO | 2018/05/30

REPOSITORIES: GEO

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The arginine methyltransferase CARM1 represses p300•ACT•CREM? activity and is required for spermiogenesis.

Project description:CARM1 is a protein arginine methyltransferase (PRMT) that has been firmly implicated in transcriptional regulation. However, the molecular mechanisms by which CARM1 orchestrates transcriptional regulation are not fully understood, especially in a tissue-specific context. We found that Carm1 is highly expressed in the mouse testis and localizes to the nucleus in spermatids, suggesting an important role for Carm1 in spermiogenesis. Using a germline-specific conditional Carm1 knockout mouse model, we found that it is essential for the late stages of haploid germ cell development. Loss of Carm1 led to a low sperm count and deformed sperm heads that can be attributed to defective elongation of round spermatids. RNA-seq analysis of Carm1-null spermatids revealed that the deregulated genes fell into similar categories as those impacted by p300-loss, thus providing a link between Carm1 and p300. Importantly, p300 has long been known to be a major Carm1 substrate. We found that CREM?, a key testis-specific transcription factor, associates with p300 through its activator, ACT, and that this interaction is negatively regulated by the methylation of p300 by Carm1. Thus, high nuclear Carm1 levels negatively impact the p300•ACT•CREM? axis during late stages of spermiogenesis.

| S-EPMC5961101 | biostudies-literature

The arginine methyltransferase CARM1 represses p300•ACT•CREMt axis and is required for spermiogenesis

Project description:The arginine methyltransferase CARM1 represses p300•ACT•CREMt axis and is required for spermiogenesis

| PRJNA422106 | ENA

A specific CBP/p300-dependent gene expression program drives the metabolic remodelling in late stages of spermatogenesis.

Project description:Histone hyperacetylation is thought to drive the replacement of histones by transition proteins that occurs in elongating spermatids after a general shut-down of transcription. The molecular machineries underlying this histone hyperacetylation remain still undefined. Here we focused our attention on the role of Cbp and p300 in histone hyperacetylation and in the preceding late gene transcriptional activity in elongating spermatids. A strategy was designed to partially deplete Cbp and p300 in elongating spermatids. These cells progressed normally through spermiogenesis and showed normal histone hyperacetylation and removal. However, a genome-wide transcriptomic analysis, performed in the round and elongating spermatids, revealed the existence of a gene regulatory circuit encompassing genes presenting high expression levels in pre-meiotic cells, undergoing a repressed state in spermatocytes and early post-meiotic cells, but becoming reactivated in elongating spermatids, just prior to the global shut-down of transcription. Interestingly, this group of genes was over-represented within the genes affected by Cbp/p300 knock-down and were all involved in metabolic remodelling. This study revealed the occurrence of a tightly regulated Cbp/p300-dependent gene expression program that drives a specific metabolic state both in progenitor spermatogenic cells and in late transcriptionally active spermatids and confirmed a special link between Cpb/p300 and cell metabolism programming previously shown in somatic cells. Total RNA were obtained from post meiotic male germ cells (round spermatids and condensing spermatids) of adult mice either wild-type or with a double knock down of Cbp/P300 in post-meiotic cells. In each experiments, 6 replicates of each genotype and cell type were used.

2014-03-12 | E-GEOD-55767 | biostudies-arrayexpress

A specific CBP/p300-dependent gene expression program drives the metabolic remodelling in late stages of spermatogenesis.

2014-03-12 | GSE55767 | GEO

mNET sequencing facilitates identification of native elongating transcripts in control and Carm1 KO melanoma cells

Project description:We investigated whether RNA Pol II mediated transcription was altered in Carm1 KO compared to control KO tumor cells. We examined p-Ser2 CTD Pol II relative to total CTD Pol II using mammalian native elongating transcript sequencing (mNET-Seq) (Nojima et al., 2016). Inactivation of the Carm1 gene substantially increased the normalized read density of p-Ser2 CTD Pol II tags relative total Pol II tags. These data provide evidence for altered transcriptional regulation in Carm1 deficient cells.

2022-01-31 | GSE148905 | GEO

Histone arginine methyltransferase CARM1 Is Crucial for Epigenetic Regulation of Starvation-induced Autophagy

Project description:Autophagy is a highly conserved self-digestion process, essential to maintain homeostasis and viability in response to nutrient starvation. Although the components of autophagy in the cytoplasm have been well-studied, molecular basis for the epigenetic regulation of autophagy is poorly understood. Here, we identify histone arginine methyltransferase CARM1 as a critical component of autophagy. We found that nutrient starvation increased CARM1 protein level and subsequently histone H3R17 dimethylation. Genome-wide analyses reveal that CARM1 exerts transcriptional coactivator function on autophagy-related genes and lysosomal genes through TFEB. Our findings demonstrate a previously unrecognized role of CARM1-dependent histone arginine methylation as a critical nuclear event of autophagy.

2016-06-17 | GSE72901 | GEO

Epigenetic regulation of cardiac maturation by arginine methyltransferase Carm1 (RNA-Seq)

Project description:Genome-wide transcriptome analysis of the neonatal control and Carm1 mutant hearts

2023-12-26 | GSE197196 | GEO

Epigenetic regulation of cardiac maturation by arginine methyltransferase Carm1 (ATAC-Seq)

Project description:Analysis of genome-wide chromatin accessibility of the neonatal control and Carm1 mutant hearts

2023-12-26 | GSE197194 | GEO

Epigenetic regulation of cardiac maturation by arginine methyltransferase Carm1 [RNA-Seq 2]

Project description:Transcriptome profile of Carm1 KO and Wildtype neonatal heart cardiomyocyte

2023-12-26 | GSE212981 | GEO

Transcription Factor RFX2 Is a Key Regulator of Mouse Spermiogenesis

Project description:To identify RFX2-dependent genes during spermatogenesis, We chose 24-day-old wild-type and mutant testes samples. Spermiogenesis in mutants was normal before this time point while massive round spermatids detached from the tubules thereafter. RNAs were isolated from the total testicular cells.

2017-02-09 | GSE74961 | GEO

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