Transcription factor Gfi-1 induced by G-CSF is a negative regulator of CXCR4 in myeloid cells

Authors:
De La Luz Sierra M, Gasperini P, McCormick PJ, Zhu J, Tosato G
In:
Source: Blood
Publication Date: (2007)
Issue: 110(7): 2276-85
Research Area:
Immunotherapy / Hematology
Cells used in publication:
32D
Species: mouse
Tissue Origin: bone marrow
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
The mechanisms underlying G-CSF-induced mobilization of granulocytic lineage cells from the bone marrow to the peripheral blood remain elusive. We provide evidence that the transcriptional repressor Gfi-1 is involved in G-CSF-induced mobilization of granulocytic lineage cells from the bone marrow to the peripheral blood. We show that in vitro and in vivo G-CSF promotes expression of Gfi-1 and down-regulates expression of CXCR4, a chemokine receptor essential for the retention of hematopoietic stem cells and granulocytic cells in the bone marrow. Gfi-1 binds to DNA sequences upstream of the CXCR4 gene and represses CXCR4 expression in myeloid lineage cells. As a consequence, myeloid cell responses to the CXCR4 unique ligand SDF-1 are reduced. Thus, Gfi-1 not only regulates hematopoietic stem cell function and myeloid cell development but also likely promotes the release of granulocytic lineage cells from the bone marrow to the peripheral blood by reducing CXCR4 expression and function.