LYSP100-ASSOCIATED NUCLEAR DOMAINS (LANDS) - DESCRIPTION OF A NEW CLASS OF SUBNUCLEAR STRUCTURES AND THEIR RELATIONSHIP TO PML NUCLEAR-BODIES

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-RA R alpha fusion oncoprotein. The PML gene product has been localized to subnuclear dot-like structures variously termed PODs, ND10s, Kr bodie s, or PML nuclear bodies (PML NBs), The present study describes the cl oning of a lymphoid-restricted gene, LYSP100, that is homologous to an other protein that localizes to PML NBs, SP100. In addition to SP100 h omology regions, one LYSP100 cDNA isoform contains a bromodomain and a PHD/TTC domain, which are present in a variety of transcriptional reg ulatory proteins. By immunofluorescence, LYSP100 was localized to nucl ear dots that were surprisingly largely nonoverlapping with PML NBs. H owever, a minority of LYSP100 nuclear dots exactly colocalized with PM L and SP100. We term the LYSP100 structures ''LANDs,'' for LYSP100-ass ociated nuclear domains, Although LYSP100 is expressed only in lymphoi d 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 s tructures characteristic of PML NBs, LANDs were most often found in th e nucleoplasm, but were also found at the nuclear membrane and in the cytoplasm, suggesting that these structures may traffic between the cy toplasm and the nucleus. By double-immunogold labeling of PML and LYSP 100, 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. (C) 1996 by The American Society of Hematology.