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

Abstract:

:The mechanisms underlying granulocyte-colony stimulating factor (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 growth factor independence-1 (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 probably promotes the release of granulocytic lineage cells from the bone marrow to the peripheral blood by reducing CXCR4 expression and function.

journal_name

Blood

journal_title

Blood

authors

De La Luz Sierra M,Gasperini P,McCormick PJ,Zhu J,Tosato G

doi

10.1182/blood-2007-03-081448

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

2276-85

issue

7

eissn

0006-4971

issn

1528-0020

pii

blood-2007-03-081448

journal_volume

110

pub_type

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