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

First Author  Kwon OH Year  2005
Journal  Biochem Biophys Res Commun Volume  335
Issue  2 Pages  437-46
PubMed ID  16083856 Mgi Jnum  J:100358
Mgi Id  MGI:3588030 Doi  10.1016/j.bbrc.2005.07.092
Citation  Kwon OH, et al. (2005) The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors. Biochem Biophys Res Commun 335(2):437-46
abstractText  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 kappaB (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.
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