The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors

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Title
The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors
Author(s)
O H Kwon; C K Lee; Young Ik Lee; S G Paik; Hyun Jun Lee
Bibliographic Citation
Biochemical and Biophysical Research Communications, vol. 335, no. 2, pp. 437-446
Publication Year
2005
Abstract
Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic transcription factor PU.1 is critical for osteoclastogenesis; however, the molecular mechanisms of PU.1-regulated osteoclastogenesis have not been explored. Here, we present evidence that the receptor activator of nuclear factor κB (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1-/- progenitor cells failed to express the RANK gene and reconstitution of PU.1 in these cells induced RANK expression. Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented the RANK gene expression. To explore the regulatory mechanism of the RANK gene expression by PU.1, we have cloned the human RANK promoter. Transient transfection assays have revealed that the 2.2-kb RANK promoter was functional in a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates the RANK gene transcription and this may represent one of the key roles of PU.1 in osteoclast differentiation.
Keyword
differentiationhematopoiesisM-CSFosteoclastpromoterPU.1RANKtranscription factor
ISSN
0006-291X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bbrc.2005.07.092
Type
Article
Appears in Collections:
Ochang Branch Institute > Natural Medicine Research Center > 1. Journal Articles
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