Transcriptional profiling during the early differentiation of granulocyte and monocyte progenitors controlled by conditional versions of the E2a-Pbx1 oncoprotein.

摘要: The E2a-Pbx1 oncoprotein of human pre-B cell leukemia prevents differentiation and maintains continued division in cultured myeloid progenitors. Previously, estrogen-dependent forms were generated that immortalized neutrophil (ECoM-G cells) or monocyte (ECoM-M progenitors permitted their terminal upon estrogen withdrawal. Here, representational difference analysis (RDA) Affymetrix array are used to identify changes gene expression accompany the early these cells. promoters genes, whose inactivation, integrate biochemical mechanism through which arrests division. Inactivation caused 10- 80-fold up regulation a small subset genes (MRP8, Cnlp, NB1, Bactenecin, YM1, Stefin 1, Lipocortin, Lactoferrin, gp91 phox Ly6-G) 10-fold down TLE1 corepressor gene, as well group expressed dividing cells (c-Myc, Nucleophosmin, Spermidine synthase, NOP56, Hnrpa1). Transcription 97% cellular including 300 other transcription factor (21 Hox genes) varied less than 3-fold, with most varying 50%. Therefore, cycle by specific rather global transcriptional mechanism. Monocyte distinguished persistent IRF8 category characterized "interferon-stimulated" (ISG15, ISG20, Ifit1, Ifi202a, Ifi203, IfiS204, Ifi204-related, IRF7 Ly6-E.1), upregulation Lrg21 bZip during late differentiation. synchronous stage-specific regulated lines comprises model system can be starting point backtrack mechanisms oncogenesis E2a-Pbx1.