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PMID:17352693

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Citation

Zheng, L, Iohara, K, Ishikawa, M, Into, T, Takano-Yamamoto, T, Matsushita, K and Nakashima, M (2007) Runx3 negatively regulates Osterix expression in dental pulp cells. Biochem. J. 405:69-75

Abstract

Osterix, a zinc-finger-containing transcription factor, is required for osteoblast differentiation and bone formation. Osterix is also expressed in dental mesenchymal cells of the tooth germ. However, transcriptional regulation by Osterix in tooth development is not clear. Genetic studies in osteogenesis place Osterix downstream of Runx2 (Runt-related 2). The expression of Osterix in odontoblasts overlaps with Runx3 during terminal differentiation in vivo. Runx3 down-regulates Osterix expression in mouse DPCs (dental pulp cells). Therefore the regulatory role of Runx3 on Osterix expression in tooth development was investigated. Enforced expression of Runx3 down-regulated the activity of the Osterix promoter in the human embryonic kidney 293 cell line. When the Runx3 responsive element on the Osterix promoter, located at -713 to -707 bp (site 3, AGTGGTT) relative to the cap site, was mutated, this down-regulation was abrogated. Furthermore, electrophoretic mobility-shift assay and chromatin immunoprecipitation assays in mouse DPCs demonstrated direct functional binding of Runx3 to the Osterix promoter. These results demonstrate the transcriptional regulation of Osterix expression by Runx3 during differentiation of dental pulp cells into odontoblasts during tooth development.

Links

PubMed PMC1925241 Online version:10.1042/BJ20070104

Keywords

Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins/genetics; Bone Morphogenetic Proteins/metabolism; Cell Differentiation/physiology; Cell Line; Core Binding Factor Alpha 1 Subunit/genetics; Core Binding Factor Alpha 1 Subunit/metabolism; Core Binding Factor Alpha 3 Subunit/genetics; Core Binding Factor Alpha 3 Subunit/metabolism; Dental Pulp/cytology; Dental Pulp/physiology; Gene Expression Regulation, Developmental; Humans; In Situ Hybridization; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Promoter Regions, Genetic; Protein Binding; Transcription Factors/genetics; Transcription Factors/metabolism; Transforming Growth Factor beta/genetics; Transforming Growth Factor beta/metabolism; Zinc Fingers

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RUNX2

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0001754)

Seeded From UniProt

complete

MOUSE:RUNX3

involved_in

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:RUNX3

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0001754)

Seeded From UniProt

complete

MOUSE:RUNX3

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(UBERON:0001754)

Seeded From UniProt

complete

MOUSE:RUNX3

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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