Identification of LM02 transcriptome and interactome in diffuse large B-cell lymphoma.

LM02 regulates gene expression by facilitating the formation of multipartite DNA-binding complexes. In B cells, LM02 is specifically up-regulated in the germinal center (GC) and is expressed in GC-derived non-Hodgkin lymphomas. LM02 is one of the most powerful prognostic indicators in diffuse large B-cell (DLBCL) patients. However, its function in GC B cells and DLBCL is currently unknown. In this study, we characterized the LM02 transcriptome and transcriptional complex in DLBCL cells. LM02 regulates genes implicated in kinetochore function, chromosome assembly, and mitosis. Overexpression of LM02 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LM02 complex contains some of the traditional partners, such as LDB1, E2A, HEB, Lyl1, ET02, and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LM02 interacting partners: ELK1, nuclear factor of activated T-cells (NFATd), and lymphoid enhancer-binding factorl (LEF1) proteins. Reporter assays revealed that LM02 increases transcriptional activity of NFATd and decreases transcriptional activity of LEF1 proteins. Overall, our studies identified a novel LM02 transcriptome and interactome in DLBCL and provides a platform for future elucidation of LM02 function in GC B cells and DLBCL pathogenesis. [ABSTRACT FROM AUTHOR]