TY - JOUR
T1 - Runx2/Cbfa1 functions
T2 - Diverse regulation of gene transcription by chromatin remodeling and co-regulatory protein interactions
AU - Lian, Jane B.
AU - Stein, Janet L.
AU - Stein, Gary S.
AU - van Wijnen, André J.
AU - Montecino, Martin
AU - Javed, Amjad
AU - Gutierrez, Soraya
AU - Shen, Jiali
AU - Zaidi, S. Kaleem
AU - Drissi, Hicham
PY - 2003
Y1 - 2003
N2 - Development of the osteoblast phenotype requires transcriptional mechanisms that regulate induction of a program of temporally expressed genes. Key components of gene activation, repression, and responsiveness to physiologic mediators require remodeling of the chromatin structure of a gene that renders promoter elements competent for the assembly of macromolecular transcriptional complexes. Here we review evidence that the Runx transcription factors support tissue-specific gene expression and bone formation by contributing to promoter structure, chromatin remodeling, and the integration of independent signaling pathways. In addition, we discuss the role of Runx2 in both activation and negative regulation of gene promoters (osteocalcin, bone sialoprotein, and Runx2/Cbfa1) in relation to the interaction of Runx with coregulatory proteins in distinct subnuclear foci. The modifications in chromatin organization and transcription of the osteocalcin gene that are influenced by the activities of Runx2/Cbfa1 mediated by interacting proteins (YAP, TLE, SMAD, C/EBP) are emphasized. These functional properties of Runx2 provide novel insights into the requirements for multiple levels of transcriptional control within the context of nuclear architecture to support the convergence of regulatory signals that control tissue-specific gene expression.
AB - Development of the osteoblast phenotype requires transcriptional mechanisms that regulate induction of a program of temporally expressed genes. Key components of gene activation, repression, and responsiveness to physiologic mediators require remodeling of the chromatin structure of a gene that renders promoter elements competent for the assembly of macromolecular transcriptional complexes. Here we review evidence that the Runx transcription factors support tissue-specific gene expression and bone formation by contributing to promoter structure, chromatin remodeling, and the integration of independent signaling pathways. In addition, we discuss the role of Runx2 in both activation and negative regulation of gene promoters (osteocalcin, bone sialoprotein, and Runx2/Cbfa1) in relation to the interaction of Runx with coregulatory proteins in distinct subnuclear foci. The modifications in chromatin organization and transcription of the osteocalcin gene that are influenced by the activities of Runx2/Cbfa1 mediated by interacting proteins (YAP, TLE, SMAD, C/EBP) are emphasized. These functional properties of Runx2 provide novel insights into the requirements for multiple levels of transcriptional control within the context of nuclear architecture to support the convergence of regulatory signals that control tissue-specific gene expression.
KW - Bone specific
KW - Chromatin
KW - Osteoblast
KW - Osteocalcin
KW - Runt homology domain
KW - Runx2/Cbfa1
KW - Transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=12244313406&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12244313406&partnerID=8YFLogxK
U2 - 10.1080/03008200390152232
DO - 10.1080/03008200390152232
M3 - Review article
C2 - 12952188
AN - SCOPUS:12244313406
SN - 0300-8207
VL - 44
SP - 141
EP - 148
JO - Connective Tissue Research
JF - Connective Tissue Research
IS - SUPPL. 1
ER -