ArticleThe Journal of biological chemistry2014
Loss of nucleolar histone chaperone NPM1 triggers rearrangement of heterochromatin and synergizes with a deficiency in DNA methyltransferase DNMT3A to drive ribosomal DNA transcription.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 68 citations in OpenAlex.
- Intranucleolar Invasion of Cajal Body Remnants Suppresses Ribosomal Biogenesis inbioRxiv : the preprint server for biology · 2026Article
- Nucleophosmin 1 proteins as potential therapeutic targets in non-communicable chronic inflammatory diseases: a review of pathophysiological mechanisms.Frontiers in cell and developmental biology · 2026Review
- Hierarchical interactions between nucleolar and heterochromatin condensates are mediated by a dual-affinity protein.Nature cell biology · 2025Article
- NPM1 mislocalization mediated by RNA Pol I inhibition alters chromatin landscape.bioRxiv : the preprint server for biology · 2025Article
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- Positive coactivator PC4 shows dynamic nucleolar distribution required for rDNA transcription and protein synthesis.Cell communication and signaling : CCS · 2025Article
- Abnormal nucleoli architecture and aggregate formation in nucleophosmin mutated acute myeloid leukaemia.Journal of cell science · 2025Article
- Contribution of p53-dependent and -independent mechanisms to upregulation of p21 in Fanconi anemia.PLoS genetics · 2024Article
- Human RPF1 and ESF1 in Pre-rRNA Processing and the Assembly of Pre-Ribosomal Particles: A Functional Study.Cells · 2024Article
- New Functional Motifs for the Targeted Localization of Proteins to the Nucleolus inInternational journal of molecular sciences · 2024Article
- The nucleolar protein GNL3 prevents resection of stalled replication forks.EMBO reports · 2023Article
- Affinity hierarchies and amphiphilic proteins underlie the co-assembly of nucleolar and heterochromatin condensates.Research square · 2023Article
- Nucleophosmin 1 cooperates with the methyltransferase DOT1L to preserve peri-nucleolar heterochromatin organization by regulating H3K27me3 levels and DNA repeats expression.Epigenetics & chromatin · 2023Article
- Dot1l cooperates with Npm1 to repress endogenous retrovirus MERVL in embryonic stem cells.Nucleic acids research · 2023Article
- Article
- Targeting and Monitoring Acute Myeloid Leukaemia with Nucleophosmin-1 (International journal of molecular sciences · 2023Review
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- Mutual dependency between lncRNA LETN and protein NPM1 in controlling the nucleolar structure and functions sustaining cell proliferation.Cell research · 2021Article
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Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleoli are prominent nuclear structures assembled and organized around actively transcribed ribosomal DNA (rDNA). The nucleolus has emerged as a platform for the organization of chromatin enriched for repressive histone modifications associated with repetitive DNA. NPM1 is a nucleolar protein required for the maintenance of genome stability. However, the role of NPM1 in nucleolar chromatin dynamics and ribosome biogenesis remains unclear. We found that normal fibroblasts and cancer cells depleted of NPM1 displayed deformed nucleoli and a striking rearrangement of perinucleolar heterochromatin, as identified by immunofluorescence staining of trimethylated H3K9, trimethylated H3K27, and heterochromatin protein 1γ (HP1γ/CBX3). By co-immunoprecipitation we found NPM1 associated with HP1γ and core and linker histones. Moreover, NPM1 was required for efficient tethering of HP1γ-enriched chromatin to the nucleolus. We next tested whether the alterations in perinucleolar heterochromatin architecture correlated with a difference in the regulation of rDNA. U1242MG glioma cells depleted of NPM1 presented with altered silver staining of nucleolar organizer regions, coupled to a modest decrease in H3K9 di- and trimethylation at the rDNA promoter. rDNA transcription and cell proliferation were sustained in these cells, indicating that altered organization of heterochromatin was not secondary to inhibition of rDNA transcription. Furthermore, knockdown of DNA methyltransferase DNMT3A markedly enhanced rDNA transcription in NPM1-depleted U1242MG cells. In summary, this study highlights a function of NPM1 in the spatial organization of nucleolus-associated heterochromatin.
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