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LYSP100-associated nuclear domains (LANDs): description of a new class of
subnuclear structures and their relationship to PML nuclear bodies
AL Dent, J Yewdell, F Puvion-Dutilleul, MH Koken, H de The and LM Staudt
Metabolism Branch, National Cancer Institute, National Institutes of
Health, Bethesda, MD 20892, USA.
The PML gene is fused to the retinoic acid receptor alpha (RAR alpha) gene
in t(15;17) acute promyelocytic leukemia (APL), creating a PML-RAR alpha
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 were 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.
Volume 88,
Issue 4,
pp. 1423-1426,
08/15/1996
Copyright © 1996 by The American Society of Hematology
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