TY - JOUR
T1 - Histone deacetylase co-repressor complex control of Runx2 and bone formation
AU - Nair, Aswathy K.
AU - Jensen, Eric D.
AU - Westendorf, Jennifer J.
PY - 2007
Y1 - 2007
N2 - A decade has passed since the transcription factor, Runx2, was found to be essential for osteoblast development and chondrocyte hypertrophy. During the last 10 years, our understanding of Runx2's physiological roles and the molecular mechanisms whereby it regulates gene expression to control cell-cycle progression and cellular differentiation has increased exponentially. Runx2 is expressed in osteoblasts, prehypertrophic chondrocytes, mesenchymal cells of the perichondrium, T lymphocytes, endothelial cells, and breast and prostate epithelial cells, with increased expression observed in breast and prostate carcinomas. Although Runx2 and other mammalian Runt domain proteins were originally described as transcriptional activators, they are also transcriptional repressors and thus maintain functional similarities with their Drosophila homolog, Runt. Runx2 binds a consensus DNA sequence but does not possess any enzymatic activities that directly affect chromatin structure. It alters gene expression by recruiting cofactors to gene regulatory elements. Histone deacetylases (HDACs) are among the co-repressors that interact with Runx2. In this review, we summarize data demonstrating that several HDACs and their associated proteins interact with Runx2, regulate its activity, and affect bone formation. HDACs are components of multiprotein complexes that interact with many transcription factors and are subject to regulation by extracellular signals. The elucidation of HDAC complex components that influence Runx2 activity in specific cell types and in response to various extracellular stimuli will increase our understanding of how this crucial transcription factor functions, and how we might be able to control its activity to influence bone formation or reduce bone disease associated with cancer metastasis.
AB - A decade has passed since the transcription factor, Runx2, was found to be essential for osteoblast development and chondrocyte hypertrophy. During the last 10 years, our understanding of Runx2's physiological roles and the molecular mechanisms whereby it regulates gene expression to control cell-cycle progression and cellular differentiation has increased exponentially. Runx2 is expressed in osteoblasts, prehypertrophic chondrocytes, mesenchymal cells of the perichondrium, T lymphocytes, endothelial cells, and breast and prostate epithelial cells, with increased expression observed in breast and prostate carcinomas. Although Runx2 and other mammalian Runt domain proteins were originally described as transcriptional activators, they are also transcriptional repressors and thus maintain functional similarities with their Drosophila homolog, Runt. Runx2 binds a consensus DNA sequence but does not possess any enzymatic activities that directly affect chromatin structure. It alters gene expression by recruiting cofactors to gene regulatory elements. Histone deacetylases (HDACs) are among the co-repressors that interact with Runx2. In this review, we summarize data demonstrating that several HDACs and their associated proteins interact with Runx2, regulate its activity, and affect bone formation. HDACs are components of multiprotein complexes that interact with many transcription factors and are subject to regulation by extracellular signals. The elucidation of HDAC complex components that influence Runx2 activity in specific cell types and in response to various extracellular stimuli will increase our understanding of how this crucial transcription factor functions, and how we might be able to control its activity to influence bone formation or reduce bone disease associated with cancer metastasis.
KW - AML-3
KW - Cbfa1
KW - HDAC
KW - HDAC inhibitors
KW - Osteoblasts
KW - PEBP2aA
UR - http://www.scopus.com/inward/record.url?scp=34249994607&partnerID=8YFLogxK
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U2 - 10.1615/CritRevEukarGeneExpr.v17.i3.20
DO - 10.1615/CritRevEukarGeneExpr.v17.i3.20
M3 - Review article
C2 - 17725488
AN - SCOPUS:34249994607
SN - 1045-4403
VL - 17
SP - 187
EP - 196
JO - Critical Reviews in Eukaryotic Gene Expression
JF - Critical Reviews in Eukaryotic Gene Expression
IS - 3
ER -