Hes1 stimulates transcriptional activity of Runx2 by increasing protein stabilization during osteoblast differentiation.
Runt-related transcription factor 2 (Runx2) is a key transcription factor for osteogenic gene expression and osteoblast differentiation. In order to maintain bone homeostasis, the transcriptional activity of Runx2 is tightly modulated by many intra- and extra-cellular factors. Here, we reveal the mechanism by which Hairy Enhancer of Split1 (Hes1) regulates the transcriptional activity of Runx2, and elucidate the potential role of Hes1 during osteoblast differentiation. Coexpression of Hes1 with Runx2 promoted an increase in Runx2 protein levels by increasing the half-life of Runx2; Hes1 thereby augmented the formation of a Runx2-DNA complex at Runx2 target sites. During osteoblast differentiation, the retroviral overexpression of Hes1 accelerated osteogenesis and stimulated the expression of osteogenic marker genes, including osteopontin and type 1 collagen. Taken together, these results suggest that Hes1 augments the protein level and transcriptional activity of Runx2, resulting in the stimulation of osteoblast differentiation.
Suh
Jung Hee
JH
Department of Biological Sciences, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-742, Republic of Korea.
Lee
Hyun Woo
HW
Lee
Joo-Won
JW
Kim
Jae Bum
JB
D016475:3T3 Cells; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000494:pharmacology*; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006207:Half-Life; D018398:Homeodomain Proteins / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D004247:DNA; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C078493:HES1 protein, human