Runx2: A master organizer of gene transcription in developing and maturing osteoblasts

Runx2 is essential for osteoblast development and proper bone formation. A member of the Runt domain family of transcription factors, Runx2 binds specific DNA sequences to regulate transcription of numerous genes and thereby control osteoblast development from mesenchymal stem cells and maturation i...

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Bibliographic Details
Published in:Birth defects research. Part C. Embryo today 2005-09, Vol.75 (3), p.213-225
Main Authors: Schroeder, Tania M., Jensen, Eric D., Westendorf, Jennifer J.
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Bone Neoplasms - metabolism
Cbfa1
Cell Nucleus - metabolism
DNA - metabolism
Gene Expression Regulation, Developmental
Humans
Models, Biological
Neoplasm Metastasis
Neoplasms - metabolism
nuclear matrix
Nuclear Matrix - metabolism
Osteoblasts - metabolism
Osteocytes - metabolism
osteogenesis
Promoter Regions, Genetic
Protein Binding
Protein Isoforms
Protein Structure, Tertiary
runt domain
Signal Transduction
Transcription, Genetic
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Summary:Runx2 is essential for osteoblast development and proper bone formation. A member of the Runt domain family of transcription factors, Runx2 binds specific DNA sequences to regulate transcription of numerous genes and thereby control osteoblast development from mesenchymal stem cells and maturation into osteocytes. Although necessary for gene transcription and osteoblast development, Runx2 is not sufficient for optimal gene expression or bone formation. Runx2 cooperates with numerous proteins, including transcription factors and cofactors, is posttranslationally modified, and associates with the nuclear matrix to integrate a variety of signals and organize crucial events during osteoblast development and maturation. Consistent with its role as a master organizer, alterations in Runx2 expression levels are associated with skeletal diseases. Runx2 haploinsufficiency causes cleidocranial dysplasia, while Runx2 overexpression is common in many bone‐metastatic cancers. In this review, we summarize the molecular mechanisms by which Runx2 integrates signals through coregulatory interactions, and discuss how its role as a master organizer may shift depending on promoter structure, developmental cues, and cellular context. Birth Defects Research (Part C) 75:213–225, 2005. © 2005 Wiley‐Liss, Inc.
ISSN:1542-975X
1542-9768
DOI:10.1002/bdrc.20043