Abstract
Notch signaling is required for multiple aspects of tissue and cell differentiation. In this study, we identified zinc finger protein 64 (Zfp64) as a novel coactivator of Notch1. Zfp64 is associated with the intracellular domain of Notch1, recruited to the promoters of the Notch target genes Hes1 and Hey1, and transactivates them. Zfp64 expression is under the control of Runx2, and is upregulated by direct transactivation of its promoter. Zfp64 suppresses the myogenic differentiation of C2C12 cells and promotes their osteoblastic differentiation. Our data demonstrate two functions of Zfp64: (1) it is a downstream target of Runx2 and, (2) its cognate protein acts as a coactivator of Notch1, which suggests that Zfp64 mediates mesenchymal cell differentiation by modulating Notch signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Cycle Proteins / metabolism
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Cell Differentiation*
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Cell Line
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Core Binding Factor Alpha 1 Subunit / metabolism*
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DNA-Binding Proteins / metabolism*
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Homeodomain Proteins / metabolism
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Humans
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Mesenchymal Stem Cells / cytology*
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Mesenchymal Stem Cells / metabolism
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Mesoderm / metabolism*
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Mice
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Molecular Sequence Data
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Nuclear Proteins / metabolism*
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Receptor, Notch1 / metabolism*
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Signal Transduction
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Transcription Factor HES-1
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Transcription Factors / metabolism*
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Transcriptional Activation
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Up-Regulation
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Cell Cycle Proteins
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Core Binding Factor Alpha 1 Subunit
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DNA-Binding Proteins
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Hes1 protein, mouse
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Hey1 protein, mouse
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Homeodomain Proteins
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Notch1 protein, mouse
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Nuclear Proteins
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Receptor, Notch1
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Runx2 protein, mouse
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Transcription Factor HES-1
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Transcription Factors
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Zfp64 protein, mouse