LYSP100-associated nuclear domains (LANDs): Description of a new class of subnuclear structures and their relationship to PML nuclear bodies

Alexander Dent, Jonathan Yewdell, Francine Puvion-Dutilleul, Marcel H M Koken, Hugues De The, Louis M. Staudt

Research output: Contribution to journalArticle

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Abstract

The PML gene is fused to the retinoic acid receptor α (RARα) gene in t(15; 17) acute promyelocytic leukemia (APL), creating a PML-RARα fusion oncoprotein. The PML gene product has been localized to subnuclear dot-like structures variously termed PODs, ND10s, Kr bodies, or PML nuclear bodies (PML NBs). The present study describes the cloning of a lymphoid-restricted gene, LYSP100, that is homologous to another protein that localizes to PML NBs, SP100. In addition to SP100 homology regions, one LYSP100 cDNA isoform contains a bromodomain and a PHD/TTC domain, which are present in a variety of transcriptional regulatory proteins. By immunofluorescence, LYSP100 was localized to nuclear dots that were surprisingly largely nonoverlapping with PML NBs. However, a minority of LYSP100 nuclear dots exactly colocalized with PML and SP100. We term the LYSP100 structures 'LANDs,' for LYSP100-associated nuclear domains. Although LYSP100 is expressed only in lymphoid cells, LANDs could be visualized in HeLa cells by transfection of a LYSP100 cDNA. Immunoelectron microscopy revealed LANDs to be globular, electron-dense structures morphologically distinct from the annular structures characteristic of PML NBs. LANDs were most often found in the nucleoplasm, but were also found at the nuclear membrane and in the cytoplasm, suggesting that these structures may traffic between the cytoplasm and the nucleus. By double-immunogold labeling of PML and LYSP100, some LANDs ware shown to contain both PML and LYSP100. Thus, PML is localized to a second subnuclear domain that is morphologically and biochemically distinct from PML NBs.

Original languageEnglish (US)
Pages (from-to)1423-1436
Number of pages14
JournalBlood
Volume88
Issue number4
StatePublished - Aug 15 1996
Externally publishedYes

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Genes
Retinoic Acid Receptors
Cytoplasm
Complementary DNA
Acute Promyelocytic Leukemia
Immunoelectron Microscopy
Cloning
Oncogene Proteins
Nuclear Envelope
HeLa Cells
Labeling
Fluorescent Antibody Technique
Transfection
Organism Cloning
Microscopic examination
Protein Isoforms
Proteins
Fusion reactions
Lymphocytes
Electrons

ASJC Scopus subject areas

  • Hematology

Cite this

Dent, A., Yewdell, J., Puvion-Dutilleul, F., Koken, M. H. M., De The, H., & Staudt, L. M. (1996). LYSP100-associated nuclear domains (LANDs): Description of a new class of subnuclear structures and their relationship to PML nuclear bodies. Blood, 88(4), 1423-1436.

LYSP100-associated nuclear domains (LANDs) : Description of a new class of subnuclear structures and their relationship to PML nuclear bodies. / Dent, Alexander; Yewdell, Jonathan; Puvion-Dutilleul, Francine; Koken, Marcel H M; De The, Hugues; Staudt, Louis M.

In: Blood, Vol. 88, No. 4, 15.08.1996, p. 1423-1436.

Research output: Contribution to journalArticle

Dent, A, Yewdell, J, Puvion-Dutilleul, F, Koken, MHM, De The, H & Staudt, LM 1996, 'LYSP100-associated nuclear domains (LANDs): Description of a new class of subnuclear structures and their relationship to PML nuclear bodies', Blood, vol. 88, no. 4, pp. 1423-1436.
Dent, Alexander ; Yewdell, Jonathan ; Puvion-Dutilleul, Francine ; Koken, Marcel H M ; De The, Hugues ; Staudt, Louis M. / LYSP100-associated nuclear domains (LANDs) : Description of a new class of subnuclear structures and their relationship to PML nuclear bodies. In: Blood. 1996 ; Vol. 88, No. 4. pp. 1423-1436.
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