title: Runx2/Cbfa1 functions: diverse regulation of gene transcription by chromatin remodeling and co-regulatory protein interactions.
abstract: 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 co-regulatory 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.
authors.affiliation: Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0106, USA. jane.lian@umassmed.edu
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.forename: André J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Martin
authors.initials: M
authors.lastname: Montecino
authors.forename: Amjad
authors.initials: A
authors.lastname: Javed
authors.forename: Soraya
authors.initials: S
authors.lastname: Gutierrez
authors.forename: Jiali
authors.initials: J
authors.lastname: Shen
authors.forename: S Kaleem
authors.initials: SK
authors.lastname: Zaidi
authors.forename: Hicham
authors.initials: H
authors.lastname: Drissi
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit; D050657:Core Binding Factor alpha Subunits; D005786:Gene Expression Regulation; D006801:Humans; D009363:Neoplasm Proteins; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D050659:Core Binding Factor Alpha 1 Subunit; D050657:Core Binding Factor alpha Subunits; D009363:Neoplasm Proteins; D014157:Transcription Factors; D015675:Osteocalcin