Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells
| Autor: | Wendy A. Bickmore, Jesús Espada, Ingrid Grummt, Gernot Längst, Juan C. Stockert, Helena Orozco, Angeles Juarranz, Vanessa P. Moreno, Agustín Aranda, Mario F. Fraga, Attila Németh, Santiago Ropero, Esteban Ballestar, Manel Esteller, Ana Villar-Garea, Raffaella Santoro, Lidia Lopez-Serra |
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| Rok vydání: | 2007 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
Transcription Genetic Nucleolus ADN Biology DNA Ribosomal environment and public health Epigenesis Genetic Epigènesi Histones Histone H4 Sirtuin 1 Cell Line Tumor Genetics Humans Sirtuins DNA (Cytosine-5-)-Methyltransferases Ribosomal DNA Epigenomics Fibrillarin Nucleic Acid Enzymes Genes rRNA DNA DNA Methylation Molecular biology Chromatin embryonic structures DNA methylation RNA Histone deacetylase Genètica Cell Nucleolus Gene Deletion Epigenesis |
| Zdroj: | Nucleic Acids Research Dipòsit Digital de la UB Universidad de Barcelona Espada, J, Ballestar, E, Santoro, R, Fraga, M F, Villar-Garea, A, Németh, A, Lopez-Serra, L, Ropero, S, Aranda, A, Orozco, H, Moreno, V, Juarranz, A, Stockert, J C, Längst, G, Grummt, I, Bickmore, W & Esteller, M 2007, ' Epigenetic disruption of ribosomal RNA genes and nucleolar architecture in DNA methyltransferase 1 (Dnmt1) deficient cells ', Nucleic Acids Research, vol. 35, no. 7, pp. 2191-8 . https://doi.org/10.1093/nar/gkm118 |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkm118 |
| Popis: | The nucleolus is the site of ribosome synthesis in the nucleus, whose integrity is essential. Epigenetic mechanisms are thought to regulate the activity of the ribosomal RNA (rRNA) gene copies, which are part of the nucleolus. Here we show that human cells lacking DNA methyltransferase 1 (Dnmt1), but not Dnmt33b, have a loss of DNA methylation and an increase in the acetylation level of lysine 16 histone H4 at the rRNA genes. Interestingly, we observed that SirT1, a NAD+-dependent histone deacetylase with a preference for lysine 16 H4, interacts with Dnmt1; and SirT1 recruitment to the rRNA genes is abrogated in Dnmt1 knockout cells. The DNA methylation and chromatin changes at ribosomal DNA observed are associated with a structurally disorganized nucleolus, which is fragmented into small nuclear masses. Prominent nucleolar proteins, such as Fibrillarin and Ki-67, and the rRNA genes are scattered throughout the nucleus in Dnmt1 deficient cells. These findings suggest a role for Dnmt1 as an epigenetic caretaker for the maintenance of nucleolar structure. |
| Databáze: | OpenAIRE |
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