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    Differential regulation of the two principal Runx2/Cbfa1 n-terminal isoforms in response to bone morphogenetic protein-2 during development of the osteoblast phenotype

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    Authors
    Banerjee, Chaitali
    Javed, Amjad
    Choi, Je-Yong
    Green, Jack
    Rosen, Vicki
    Van Wijnen, Andre J.
    Stein, Janet L.
    Lian, Jane B.
    Stein, Gary S.
    UMass Chan Affiliations
    Department of Cell Biology
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2001-08-23
    Keywords
    Animals; Bone Morphogenetic Proteins; Cell Aging; Cell Differentiation; Cell Division; Cells, Cultured; Core Binding Factor Alpha 1 Subunit; Gene Expression; *Gene Expression Regulation, Developmental; Mice; *Neoplasm Proteins; Osteoblasts; Phenotype; Protein Isoforms; Rats; Stem Cells; Transcription Factors; *Transforming Growth Factor beta
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    https://doi.org/10.1210/endo.142.9.8367
    Abstract
    Cbfa1/Runx2 is a transcription factor essential for bone formation and osteoblast differentiation. Two major N-terminal isoforms of Cbfa1, designated type I/p56 (PEBP2aA1, starting with the sequence MRIPV) and type II/p57 (til-1, starting with the sequence MASNS), each regulated by distinct promoters, are known. Here, we show that the type I transcript is constitutively expressed in nonosseous mesenchymal tissues and in osteoblast progenitor cells. Cbfa1 type I isoform expression does not change with the differentiation status of the cells. In contrast, the type II transcript is increased during differentiation of primary osteoblasts and is induced in osteoprogenitors and in premyoblast C2C12 cells in response to bone morphogenetic protein-2. The functional equivalence of the two isoforms in activation and repression of bone-specific genes indicates overlapping functional roles. The presence of the ubiquitous type I isoform in nonosseous cells and before bone morphogenetic protein-2 induced expression of the type II isoform suggests a regulatory role for Cbfa1 type I in early stages of mesenchymal cell development, whereas type II is necessary for osteogenesis and maintenance of the osteoblast phenotype. Our data indicate that Cbfa1 function is regulated by transcription, cellular protein levels, and DNA binding activity during osteoblast differentiation. Taken together, our studies suggest that developmental timing and cell type- specific expression of type I and type II Cbfa isoforms, and not necessarily molecular properties or sequences that reside in the N-terminus of Cbfa1, are the principal determinants of the osteogenic activity of Cbfa1.
    Source

    Endocrinology. 2001 Sep;142(9):4026-39.

    DOI
    10.1210/endo.142.9.8367
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34077
    PubMed ID
    11517182
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    Link to article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1210/endo.142.9.8367
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