title: Identification of LMO2 transcriptome and interactome in diffuse large B-cell lymphoma.
abstract: LMO2 regulates gene expression by facilitating the formation of multipartite DNA-binding complexes. In B cells, LMO2 is specifically up-regulated in the germinal center (GC) and is expressed in GC-derived non-Hodgkin lymphomas. LMO2 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 LMO2 transcriptome and transcriptional complex in DLBCL cells. LMO2 regulates genes implicated in kinetochore function, chromosome assembly, and mitosis. Overexpression of LMO2 in DLBCL cell lines results in centrosome amplification. In DLBCL, the LMO2 complex contains some of the traditional partners, such as LDB1, E2A, HEB, Lyl1, ETO2, and SP1, but not TAL1 or GATA proteins. Furthermore, we identified novel LMO2 interacting partners: ELK1, nuclear factor of activated T-cells (NFATc1), and lymphoid enhancer-binding factor1 (LEF1) proteins. Reporter assays revealed that LMO2 increases transcriptional activity of NFATc1 and decreases transcriptional activity of LEF1 proteins. Overall, our studies identified a novel LMO2 transcriptome and interactome in DLBCL and provides a platform for future elucidation of LMO2 function in GC B cells and DLBCL pathogenesis.
authors.affiliation: Division of Hematology-Oncology, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Cubedo
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gentles
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Huang
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
authors.forename: Shruti
authors.initials: S
authors.lastname: Bhatt
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Lu
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Jiang
authors.forename: Isabel
authors.initials: I
authors.lastname: Romero-Camarero
authors.forename: Aharon
authors.initials: A
authors.lastname: Freud
authors.forename: Shuchun
authors.initials: S
authors.lastname: Zhao
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bacchi
authors.forename: Jose A
authors.initials: JA
authors.lastname: Martínez-Climent
authors.forename: Isidro
authors.initials: I
authors.lastname: Sánchez-García
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.forename: Izidore S
authors.initials: IS
authors.lastname: Lossos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018385:Centrosome / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D059467:Transcriptome; D014166:Transferases; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109420:DLEU2 lncRNA, human; D060588:LIM Domain Proteins; C085117:LMO2 protein, human; D011518:Proto-Oncogene Proteins; D062085:RNA, Long Noncoding; D025521:Tumor Suppressor Proteins; D014166:Transferases