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- W2002232640 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. 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." @default.
- W2002232640 created "2016-06-24" @default.
- W2002232640 creator A5035824635 @default.
- W2002232640 creator A5048855545 @default.
- W2002232640 creator A5067877573 @default.
- W2002232640 date "2014-12-01" @default.
- W2002232640 modified "2023-10-18" @default.
- W2002232640 title "Loss of Nucleolar Histone Chaperone NPM1 Triggers Rearrangement of Heterochromatin and Synergizes with a Deficiency in DNA Methyltransferase DNMT3A to Drive Ribosomal DNA Transcription" @default.
- W2002232640 cites W1255676896 @default.
- W2002232640 cites W1493424835 @default.
- W2002232640 cites W1964232579 @default.
- W2002232640 cites W1966415514 @default.
- W2002232640 cites W1967501957 @default.
- W2002232640 cites W1969069329 @default.
- W2002232640 cites W1978981036 @default.
- W2002232640 cites W1979818557 @default.
- W2002232640 cites W1979891719 @default.
- W2002232640 cites W1980373840 @default.
- W2002232640 cites W1983751803 @default.
- W2002232640 cites W1989949054 @default.
- W2002232640 cites W1990414704 @default.
- W2002232640 cites W1992753961 @default.
- W2002232640 cites W1993463805 @default.
- W2002232640 cites W1999962568 @default.
- W2002232640 cites W2001866617 @default.
- W2002232640 cites W2002373110 @default.
- W2002232640 cites W2004446968 @default.
- W2002232640 cites W2008722912 @default.
- W2002232640 cites W2011068062 @default.
- W2002232640 cites W2011769944 @default.
- W2002232640 cites W2012387063 @default.
- W2002232640 cites W2012848479 @default.
- W2002232640 cites W2013142460 @default.
- W2002232640 cites W2014674316 @default.
- W2002232640 cites W2019845267 @default.
- W2002232640 cites W2020905873 @default.
- W2002232640 cites W2021080331 @default.
- W2002232640 cites W2021709122 @default.
- W2002232640 cites W2022590421 @default.
- W2002232640 cites W2023967169 @default.
- W2002232640 cites W2028500280 @default.
- W2002232640 cites W2029020439 @default.
- W2002232640 cites W2032054503 @default.
- W2002232640 cites W2037149555 @default.
- W2002232640 cites W2039260633 @default.
- W2002232640 cites W2039463309 @default.
- W2002232640 cites W2043822218 @default.
- W2002232640 cites W2045914521 @default.
- W2002232640 cites W2046640992 @default.
- W2002232640 cites W2046857670 @default.
- W2002232640 cites W2048311842 @default.
- W2002232640 cites W2049039063 @default.
- W2002232640 cites W2060683701 @default.
- W2002232640 cites W2065529250 @default.
- W2002232640 cites W2070586969 @default.
- W2002232640 cites W2070932926 @default.
- W2002232640 cites W2071061394 @default.
- W2002232640 cites W2072742925 @default.
- W2002232640 cites W2073481051 @default.
- W2002232640 cites W2074522207 @default.
- W2002232640 cites W2078241711 @default.
- W2002232640 cites W2078448904 @default.
- W2002232640 cites W2080363706 @default.
- W2002232640 cites W2082225623 @default.
- W2002232640 cites W2082627145 @default.
- W2002232640 cites W2082843075 @default.
- W2002232640 cites W2089007226 @default.
- W2002232640 cites W2091405727 @default.
- W2002232640 cites W2092594973 @default.
- W2002232640 cites W2094754719 @default.
- W2002232640 cites W2098278518 @default.
- W2002232640 cites W2098784640 @default.
- W2002232640 cites W2099454327 @default.
- W2002232640 cites W2105298120 @default.
- W2002232640 cites W2119795320 @default.
- W2002232640 cites W2123971022 @default.
- W2002232640 cites W2124552631 @default.
- W2002232640 cites W2131823236 @default.
- W2002232640 cites W2133959309 @default.
- W2002232640 cites W2135318926 @default.
- W2002232640 cites W2142412083 @default.
- W2002232640 cites W2142965179 @default.
- W2002232640 cites W2145415478 @default.
- W2002232640 cites W2152116027 @default.
- W2002232640 cites W2155781667 @default.
- W2002232640 cites W2156506178 @default.
- W2002232640 cites W2158412075 @default.
- W2002232640 cites W2326240230 @default.
- W2002232640 cites W2327197426 @default.
- W2002232640 cites W2410322297 @default.
- W2002232640 doi "https://doi.org/10.1074/jbc.m114.569244" @default.
- W2002232640 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4263867" @default.
- W2002232640 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25349213" @default.
- W2002232640 hasPublicationYear "2014" @default.
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