LEF-1 is a decisive transcription factor in neutrophil granulopoiesis.
We found that lymphoid enhancer-binding factor 1 (LEF-1) is a decisive transcription factor in granulopoiesis controlling proliferation, proper lineage commitment, and granulocytic differentiation via regulation of its target genes C/EBP-alpha, cyclin D1, c-myc, and survivin. Myeloid progenitor cells of patients with severe congenital neutropenia (CN) showed a severe downregulation of LEF-1 and its target genes expression. Expression of neutrophil elastase (NE) is also severely reduced in CN myeloid progenitors. Intriguingly, ELA2 gene promoter is positively regulated by direct binding of LEF-1 or LEF-1 target gene C/EBP-alpha. In summary we demonstrated that LEF-1 is not only crucial in lymphopoiesis, but also in myelopoiesis, documenting new functions of LEF-1.
Skokowa
Julia
J
Department of Pediatric Hematology and Oncology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Welte
Karl
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002454:Cell Differentiation; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009503:Neutropenia / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology*; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013577:Syndrome; D014157:Transcription Factors / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D022763:CCAAT-Enhancer-Binding Protein-alpha; C104759:HAX1 protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors