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LEF‐1 Is a Decisive Transcription Factor in Neutrophil Granulopoiesis
Author(s) -
SKOKOWA JULIA,
WELTE KARL
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1392.012
Subject(s) - granulopoiesis , myelopoiesis , transcription factor , myeloid , irf8 , cancer research , downregulation and upregulation , enhancer , progenitor cell , biology , lymphopoiesis , neutrophil elastase , ets transcription factor family , microbiology and biotechnology , gene , chemistry , immunology , genetics , stem cell , inflammation
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‐α, 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‐α. In summary we demonstrated that LEF‐1 is not only crucial in lymphopoiesis, but also in myelopoiesis, documenting new functions of LEF‐1.