The transcription factor MEF/ELF4 regulates the quiescence of primitive hematopoietic cells.
The transcriptional circuitry that regulates the quiescence of hematopoietic stem cells is largely unknown. We report that the transcription factor known as MEF (or ELF4), which is targeted by the t(X;21)(q26;q22) in acute myelogenous leukemia, regulates the proliferation of primitive hematopoietic progenitor cells at steady state, controlling their quiescence. Mef null HSCs display increased residence in G0 with reduced 5-bromodeoxyuridine incorporation in vivo and impaired cytokine-driven proliferation in vitro. Due to their increased HSC quiescence, Mef null mice are relatively resistant to the myelosuppressive effects of chemotherapy and radiation. Thus, MEF plays an important role in the decision of stem/primitive progenitor cells to divide or remain quiescent by regulating their entry to the cell cycle.
Lacorazza
H Daniel
HD
Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. hdl@bcm.tmc.edu
Yamada
Takeshi
T
Liu
Yan
Y
Miyata
Yasuhiko
Y
Sivina
Mariela
M
Nunes
Juliana
J
Nimer
Stephen D
SD
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D016026:Bone Marrow Transplantation; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D014157:Transcription Factors / Q000378:metabolism*
D000963:Antimetabolites; D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; D014157:Transcription Factors; D005472:Fluorouracil