NAT10-mediated mRNA N4-acetylcitidine (ac4C) Promotes Stemness and Leukemogenesis in Acute Myeloid Leukemia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1033527 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26561600_1.fastq.gz | Fastqsanger.gz | |||
| SRR26561600_2.fastq.gz | Fastqsanger.gz | |||
| SRR26561601_1.fastq.gz | Fastqsanger.gz | |||
| SRR26561601_2.fastq.gz | Fastqsanger.gz | |||
| SRR26561602_1.fastq.gz | Fastqsanger.gz |
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Project description:R-loop remodeling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer to sustain self-renewal and malignancy remains poorly understood. Here, we found that glioblastoma (GBM) stem cells (GSCs) display highly active R-loops compared to differentiated tumor progeny and neural stem cells (NSCs). Genome-wide mapping by R-loop RNA chromatin immunoprecipitation sequencing (RR-ChIP-seq) revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. We profiled R-loop interactomes and identified N-Acetyltransferase 10 (NAT10), an RNA N4-acetylcytidine (ac4C)-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 was overexpressed in GSCs. ac4C-specific RNA immunoprecipitation sequencing (ac4C-RIP-seq) on R-loop RNA revealed genome-wide mapping of ac4C-modified R-loops with abundant ac4C-modified R-loops that regulated the genome. NAT10 catalyzed widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating open chromatin to sustain self-renewal through core stemness regulators, including transcription factor EGR1. NAT10 knockdown suppressed proliferation and maintenance in vitro and attenuated tumor growth in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting cancer.
2026-04-10 | PXD077002 | Pride
Project description:R-loop remodelling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer stem cells to sustain self-renewal and malignancy remains poorly understood. In this study, we found that glioblastoma stem cells (GSCs) maintain a highly active R-loop state compared to their differentiated progeny and normal human stem cells. Genome-wide mapping via RR-ChIP-seq revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. To identify key regulators, we profiled the R-loop interactome and identified N-Acetyltransferase 10 (NAT10), an established RNA ac4C-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 is overexpressed in both GSCs and GBM. ac4C RIP-seq on R-loop RNA revealed abundant ac4C-modified R-loops that regulated the GSC genome. Mechanistically, NAT10 catalyzes widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating an open chromatin state to sustain GSC self-renewal through controlling key stemness regulators such as the transcription factor EGR1. NAT10 knockdown suppressed GSC proliferation and maintenance in vitro and attenuated GBM progression in orthotopic xenograft models in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor Remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting this axis in GBM.
2026-04-08 | GSE307596 | GEO
Project description:R-loop remodelling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer stem cells to sustain self-renewal and malignancy remains poorly understood. In this study, we found that glioblastoma stem cells (GSCs) maintain a highly active R-loop state compared to their differentiated progeny and normal human stem cells. Genome-wide mapping via RR-ChIP-seq revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. To identify key regulators, we profiled the R-loop interactome and identified N-Acetyltransferase 10 (NAT10), an established RNA ac4C-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 is overexpressed in both GSCs and GBM. ac4C RIP-seq on R-loop RNA revealed abundant ac4C-modified R-loops that regulated the GSC genome. Mechanistically, NAT10 catalyzes widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating an open chromatin state to sustain GSC self-renewal through controlling key stemness regulators such as the transcription factor EGR1. NAT10 knockdown suppressed GSC proliferation and maintenance in vitro and attenuated GBM progression in orthotopic xenograft models in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor Remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting this axis in GBM.
2026-04-08 | GSE307600 | GEO
Project description:R-loop remodelling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer stem cells to sustain self-renewal and malignancy remains poorly understood. In this study, we found that glioblastoma stem cells (GSCs) maintain a highly active R-loop state compared to their differentiated progeny and normal human stem cells. Genome-wide mapping via RR-ChIP-seq revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. To identify key regulators, we profiled the R-loop interactome and identified N-Acetyltransferase 10 (NAT10), an established RNA ac4C-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 is overexpressed in both GSCs and GBM. ac4C RIP-seq on R-loop RNA revealed abundant ac4C-modified R-loops that regulated the GSC genome. Mechanistically, NAT10 catalyzes widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating an open chromatin state to sustain GSC self-renewal through controlling key stemness regulators such as the transcription factor EGR1. NAT10 knockdown suppressed GSC proliferation and maintenance in vitro and attenuated GBM progression in orthotopic xenograft models in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor Remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting this axis in GBM.
2026-04-08 | GSE307594 | GEO
Project description:R-loop remodelling dynamically regulates chromatin states and gene expression; however, its exploitation by cancer stem cells to sustain self-renewal and malignancy remains poorly understood. In this study, we found that glioblastoma stem cells (GSCs) maintain a highly active R-loop state compared to their differentiated progeny and normal human stem cells. Genome-wide mapping via RR-ChIP-seq revealed cell-specific enrichment and spatial accumulation of R-loops at promoter-proximal regions in GSCs, correlating with active transcription and open chromatin states. To identify key regulators, we profiled the R-loop interactome and identified N-Acetyltransferase 10 (NAT10), an established RNA ac4C-modifying enzyme, as a high-affinity R-loop-binding protein in GSCs. Driven by transcriptional activation via OLIG1, NAT10 is overexpressed in both GSCs and GBM. ac4C RIP-seq on R-loop RNA revealed abundant ac4C-modified R-loops that regulated the GSC genome. Mechanistically, NAT10 catalyzes widespread ac4C deposition on the RNA stand of R-loops, stabilizing promoter-associated R-loops, and facilitating an open chromatin state to sustain GSC self-renewal through controlling key stemness regulators such as the transcription factor EGR1. NAT10 knockdown suppressed GSC proliferation and maintenance in vitro and attenuated GBM progression in orthotopic xenograft models in vivo. Pharmacological inhibition of NAT10/ac4C-modified R-loops using the small-molecule inhibitor Remodelin phenocopied NAT10 genetic targeting, demonstrating therapeutic promise for targeting this axis in GBM.
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Project description:NAT10-Dependent N4-acetylcytidine (ac4C) on R-loops Drive Glioblastoma Tumorigenesis and Stemness [ac4C-RIP-seq]
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Project description:NAT10-Dependent N4-acetylcytidine (ac4C) on R-loops Drive Glioblastoma Tumorigenesis and Stemness
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Project description:Pancreatic cancer is a lethal diease with high tendency of metastasis. Howerver, the mechanisms of pancreatic cancer are sitill unclear. To explore the roles of N4-acetylation (ac4C) RNA modification and its involved N-Acetyltransferase 10 (NAT10) in pancreatic ductal adenocarcinoma (PDAC), we performed profiling by high throughput sequencing. In this study, we investigate the effects of NAT10 knockdown on N4-acetylcytidine (ac4C) modification in mRNA within PANC-1 cells using ac4C-seq. By employing RNA interference to specifically knock down NAT10 expression in PANC-1 cells, we aim to elucidate its impact on ac4C RNA modifications, which have been implicated in various cellular processes and cancer progression. Total RNA was extracted and mRNA was captured and treated with sodium borohydride (NaBH4) for detection of ac4C sites.Following library preparation, sequencing was performed on an Illumina Novaseq 6000 platform. Bioinformatics analyses identified significant changes in ac4C modification patterns due to NAT10 depletion. This dataset provides a valuable resource for further exploration of ac4C modifications in mRNA and their role in PDAC.
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Project description:N4-acetylcytidine (ac4C), a conserved chemical modification in eukaryotic prokaryotes that is catalyzed by the N-acetyltransferase 10 (NAT10) enzyme, plays a crucial role in promoting mRNA stability and translation. However, the biological function and mechanisms of NAT10-mediated ac4C in human cancer were poorly defined. In order to investigate the regulatory mechanism of NAT10 in gastric cancer, we performed ac4C RIP-seq(acRIP-seq) analysis in AGS cells with NAT10 knockout compared with control in two repeats.
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