Expression data from siSCR and siPRMT1 ES cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE37060 | GEO | 2014/12/01
SECONDARY ACCESSION(S): PRJNA157959
REPOSITORIES: GEO
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Project description:Epigenetic modifications play important roles during the pathogenesis of multiple myeloma (MM). Here, we found that protein arginine methyltransferase 1 (PRMT1) was highly expressed in MM patients and its expression level was positively correlated with MM stages. High PRMT1 expression were notably related to adverse prognosis in MM patients. We further showed that silencing PRMT1 inhibited MM proliferation and tumorigenesis in vitro and in vivo. Mechanistically, we revealed that knockdown of PRMT1 reduced the oxidative phosphorylation (OXPHOS) of MM cells through downregulation of NDUFS6. Meanwhile, we identified that WTAP, a key component of the m6A methyltransferase complex, was methylated by PRMT1 and NDUFS6 was identified as a bona fide m6A target of WTAP. Finally, we found that PRMT1 inhibitor and bortezomib combination synergistically inhibited MM progression. Collectively, our results demonstrate that PRMT1 plays a crucial role during MM tumorigenesis and suggest that PRMT1 could be a potential therapeutic target in MM.
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Project description:Retrotransposons are widely spread in the mammalian genome and are usually silenced during development to avoid transposition-inducing mutations. But how they are repressed in embryos shortly before implantation remain to be identified, since the genome at this stage is globally hypomethylated. Here we show a histone chaperon, CAF-1, is responsible for retrotransposon silencing at the morula-blastocyst stages by depositing histone H4 lysine 20 trimethylation (H4K20me3). Knockdown of CAF-1 with a specific siRNA resulted in derepression of LINE-1, SINE-B2 and IAP associated with the decreased H4K20me3 level, and arrested embryonic development at the morula stage. The identical results were obtained with siRNAs against Suv420h1/2, H4K20 methyltransferases. Treatment with reverse transcriptase inhibitors rescued at least a part of these embryos. Thus, CAF-1 ensures the genomic integrity of preimplantation embryos by establishing repressive histone marks in the multiple retrotransposon classes. Comparative gene expression analyses using P150 knockdown (P150KD) embryos at morula stage were performed by microarray. P150KD embryos were produced with the injection of P150 siRNA into 1-cell embryos. As controls, siControl embryos were produced by the injection of control siRNA. These embryos were subjected to gene expression microarray.
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