Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions

Wang, Jayson; Shiels, Carol; Sasieni, Peter; Wu, Pei Jun; Islam, Suhail A.; Freemont, Paul S.; Sheer, Denise

doi:10.1083/jcb.200305142

Cited by 209 publications

(202 citation statements)

References 57 publications

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“…Newly synthesized RNA is associated with the periphery of ND10, and many transcriptional regulators have been shown to biochemically interact with PML (49)(50)(51). However, other studies have found no association of nascent RNA, active transcription, or general transcription factors at ND10 (45,49,52). Kiesslich et al (53) confirmed that in nonsynchronized cells the majority of nascent RNA was not associated with ND10.…”

Section: Discussionsupporting

confidence: 59%

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

Day

Baker

Lowy

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

218

277

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Previous studies have suggested that most papillomaviruses enter the host cell via clathrin-dependent receptor-mediated endocytosis but have not addressed later steps in viral entry. To examine these events, we followed the localization of L2 and packaged DNA after entry of infectious virions or L1͞L2 pseudovirions. Confocal microscopic analyses of HeLa cells showed a time-dependent uncoating of capsids in cytoplasmic vesicles and the accumulation of both L2 and viral DNA at distinct nuclear domains identified as nuclear domain 10 (ND10). Both L2 and the pseudogenome had a punctate distribution and localized to ND10 in promyelocytic leukemia protein (PML)-expressing cells, whereas L2 had a diffuse nuclear distribution in PML؊͞؊ cells. The number of pseudovirus-infected cells was an order of magnitude higher in the PML؉ cells compared with the PML؊͞؊ cells, and viral genome transcription after infection with authentic bovine papillomavirus virions was similarly elevated in PML؉ cells. The results identify a role for PML in the enhancement of viral infectivity in the early part of the life cycle. We propose a model in which L2 chaperones the viral genome to ND10 to efficiently initiate viral transcription.

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Section: Discussionsupporting

confidence: 59%

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

Day

Baker

Lowy

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

218

277

View full text Add to dashboard Cite

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“…Although RNA FISH and RNA interference (RNAi) experiments did not reveal a strict correlation of transcriptional activity and localization to PML-NBs, the majority of RNA transcript foci analyzed were positioned at the bodies. Furthermore, treatment of an APL cell line with all-trans retinoic acid resulted in the generation of PML-NBs and the concomitant localization of an active locus to the emergent structures (Wang et al 2004). It is therefore plausible that PML-NBs play a role in transcription, possibly as a reservoir of concentrated transcriptional regulators (Fig.…”

Section: Nuclear Bodiesmentioning

confidence: 99%

“…In support of a role in transcription, regulatory factors such as cyclic AMP response-binding protein (CBP) and retinoblastoma protein (pRB) have been shown to interact directly with PML (Ruggero et al 2000). A recent localization analysis of gene-dense domains in the human genome revealed that transcriptionally robust loci are associated with PML-NBs (Wang et al 2004). Although RNA FISH and RNA interference (RNAi) experiments did not reveal a strict correlation of transcriptional activity and localization to PML-NBs, the majority of RNA transcript foci analyzed were positioned at the bodies.…”

Section: Nuclear Bodiesmentioning

confidence: 99%

Form follows function: the genomic organization of cellular differentiation

Kosak¹,

Groudine²

2004

Genes Dev.

218

179

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The extent to which the nucleus is functionally organized has broad biological implications. Evidence supports the idea that basic nuclear functions, such as transcription, are structurally integrated within the nucleus. Moreover, recent studies indicate that the linear arrangement of genes within eukaryotic genomes is nonrandom. We suggest that determining the relationship between nuclear organization and the linear arrangement of genes will lead to a greater understanding of how transcriptomes, dedicated to a particular cellular function or fate, are coordinately regulated. Current network theories may provide a useful framework for modeling the inherent complexity the functional organization of the nucleus.Louis Sullivan, whose early efforts helped pioneer the development of the skyscraper, is considered one of the most important architects of the last century. However, it is his dictum-"form ever follows function"-for which he is perhaps best known. Just as this imperative has influenced generations of architects, the idea that structure reflects function provides a useful perspective for a biologist's view of the cell. In many ways, the structure and function of cellular and subcellular organelles are inseparable; that is, disruptions in organelle function can lead to perturbations in its structure. Upon inhibition of rRNA transcription, for example, the nucleolus becomes disordered and ultimately disappears (Leung and Lamond 2003). This integration of structure and cellular function allows for conservation of resources and facilitates regulation at multiple levels.Although a completely sequenced genome may represent a genetic blueprint, molecular biologists currently lack a key with which to fully grasp how this sequence is related to the development and subsequent maintenance of a given organism. Following Sullivan's example, a comprehensive understanding of genomic sequence may require considering its arrangement in the nucleus; the form DNA takes in the nucleus reveals not only its higher-order structure, but it may impart information regarding its function. The current paradigm of gene regulation includes the binding of site-specific transcription factors, the recruitment of cofactors and general transcription factors, and the incorporation of multiple modifications to both the DNA and the histones that organize it (Felsenfeld and Groudine 2003). This description of transcription belies its enormous complexity, fueled by an ever-increasing catalog of proteins dedicated in one way or another to its regulation. Additionally, evidence supporting the role of nuclear localization in transcriptional regulation indicates that it is insufficient to know the components of transcription . Rather, a thorough understanding of the process requires knowing its functional organization within the nucleus. In this sense, transcription should not be viewed simply as a process that turns on a specific gene, but as a process that governs within the genome an entire network of genes (a transcriptome) that gives rise to a p...

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“…Since the known partners of HP1 in heterochromatin were absent from the bright HP1 focus, and HP1 and PML proteins have been shown to associate with transcriptionally active chromatin, [33][34][35] we searched for the presence of hallmarks of active chromatin at the bright focus. The distribution of the histone H3 acetylated on K9 and K18 (data not shown), the poly-acetylated histone H4 (Figure 7b), and the phosphorylated RNA polymerase II (Figure 7c) was examined, but none of them showed any specific signal co-localizing with the bright protein focus.…”

Section: Aberrant Nuclear Distribution Of Hp1a Hp1b and Hp1c Proteinmentioning

confidence: 99%

Subcellular distribution of HP1 proteins is altered in ICF syndrome

et al. 2004

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The Immunodeficiency, Centromeric instability, and Facial (ICF) syndrome is a rare autosomal recessive disorder that results from mutations in the DNMT3B gene, encoding a DNA-methyltransferase that acts on GC-rich satellite DNAs. This syndrome is characterized by immunodeficiency, facial dysmorphy, mental retardation of variable severity and chromosomal abnormalities that essentially involve juxtacentromeric heterochromatin of chromosomes 1 and 16. These abnormalities demonstrate that hypomethylation of satellite DNA can induce alterations in the structure of heterochromatin. In order to investigate the effect of DNA hypomethylation on heterochromatin organization, we analyzed the in vivo distribution of HP1 proteins, essential components of heterochromatin, in three ICF patients. We observed that, in a large proportion of ICF G2 nuclei, all HP1 isoforms show an aberrant signal concentrated into a prominent bright focus that co-localizes with the undercondensed 1qh or 16qh heterochromatin. We found that SP100, SUMO-1 and other proteins from the promyelocytic leukemia nuclear bodies (NBs) form a large body that co-localizes with the HP1 signal. This is the first description of altered nuclear distribution of HP1 proteins in the constitutional ICF syndrome. Our results show that satellite DNA hypomethylation does not prevent HP1 proteins from associating with heterochromatin. They suggest that, at G2 phase, HP1 proteins are involved in the heterochromatin condensation and may therefore remain concentrated at these sites until the condensation is complete. They also indicate that proteins from the NB could play a role in this process. Finally, satellite DNA length polymorphism could affect the efficiency of heterochromatin condensation and thus contribute to the variability of the ICF phenotype.

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Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions

Cited by 209 publications

References 57 publications

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

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

Form follows function: the genomic organization of cellular differentiation

Subcellular distribution of HP1 proteins is altered in ICF syndrome

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