PML-containing nuclear bodies: Their spatial distribution in relation to other nuclear components

Abstract

PML-containing nuclear bodies: their spatial distribution in relation to other nuclear components Grande, M.A.; van der Kraan, K.; van Steensel, B.; Schul, W.; de The, H.; van der Voort, H.T.M.; de Jong, L.; van Driel, R. Link to publicationCitation for published version (APA): Grande, M. A., van der Kraan, K., van Steensel, B., Schul, W., de The, H., van der Voort, H. T. M., ... van Driel, R. (1996). PML-containing nuclear bodies: their spatial distribution in relation to other nuclear components. Journal of Cellular Biochemistry, 63, 280-291. 3.0.CO;2-T" class="link">https://doi.org/10.1002/(SICI)1097-4644(19961201)63:33.0.CO;2-T General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. The PML protein is a human growth suppressor concentrated in 10 to 20 nuclear bodies per nucleus (PML bodies). Disruption of the PML gene has been shown to be related to acute promyelocytic leukaemia (APL). To obtain information about the function of PML bodies we have investigated the 3D-distribution of PML bodies in the nucleus of T24 cells and compared it with the spatial distribution of a variety of other nuclear components, using fluorescence dual-labeling immunocytochemistry and confocal microscopy. Results show that PML bodies are not enriched in nascent RNA, the splicing component U2-snRNP, or transcription factors (glucocorticoid receptor, 'TFIIH, and E2F). These results show that PML bodies are not prominent sites of RNA synthesis or RNA splicing. We found that a large fraction of PML bodies (50 to 80%) is closely associated with DNA replication domains during exclusively middle-late S-phase. Furthermore, in most cells that we analysed we found at least one PML body was tightly associated with a coiled body. In the APL cell line NB4, the PML gene is fused with the RARa gene due to a chromosomal rearrangement. PML bodies have disappeared and the PML antigen, i.e., PML and the PML-RAR fusion protcin, is dispersed in a punctated pattern throughout the nucleoplasm. We showed that in NB4 cells the sites that are rich in PML antigen significantly colocalize with sites at which nascent RNA accumulates. This suggests that, in contrast to non-APL cells, in NB4 cells the PML antigen is associated with sites of transcription. The implications of these findings for the function of PML bod...

The promyelocytic leukemia (PML) protein suppresses cyclin D1 protein production by altering the nuclear cytoplasmic distribution of cyclin D1 mRNA

“…However, PML nuclear bodies do not associate with sites of active transcription and do not localize with nascent DNA (Melnick and Licht, 1999). General transcription factors like TFIIH and RNA Polymerase II do not co-localize with PML bodies (Grande et al, 1996). Consistent with these ®ndings, we observe no association between PML and RNA polymerase II (Figure 2a).…”

The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis

“…The staining presented a punctuate distribution throughout the nuclei except for the nucleoli and the perinuclear chromatin, which remained unlabelled. This pattern of labeling is specific for proteins implicated in the transcriptional process (Grande et al, 1997). For CD11/HPAF cells, a mild reactivity was detected in the nuclei.…”

Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression

“…ND10s have been proposed to act as nuclear sensors that can detect exogenously introduced proteins (6,44). It has been demonstrated that ND10s assemble at precise subnuclear locations frequently adjacent to compartments that participate in RNA processing, including Cajal bodies, cleavage bodies, and SC35-positive splicing sites (45,46). This proximity suggests that ND10 could also play a part in such events.…”