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PMID:20940257

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Citation

Takigawa, Y, Hata, K, Muramatsu, S, Amano, K, Ono, K, Wakabayashi, M, Matsuda, A, Takada, K, Nishimura, R and Yoneda, T (2010) The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9. J. Cell. Sci. 123:3780-8

Abstract

Sox9 is an essential transcription factor for chondrogenesis by regulating the expression of chondrogenic genes. However, its regulatory mechanism is not fully understood. To address this, we attempted to identify the transcriptional partners of Sox9 by screening the cDNA library of the chondrogenic cell line ATDC5 using the collagen 2α1 (Col2α1) gene promoter fused to a luciferase reporter gene. One of the positive clones encoded the Znf219 gene. Whole mount in situ hybridization experiments indicated that Znf219 mRNA was specifically expressed in the developing limb buds where Col2α1 and Sox9 were strongly expressed. Znf219 markedly enhanced the transcriptional activity of Sox9 on the Col2a1 gene promoter. In addition, Znf219 is physically associated with Sox9 and is colocalized with Sox9 in the nucleus. We also found that overexpression of Znf219 profoundly increased Sox9-induced mRNA expression of Col2a1, aggrecan and Col11a2. Consistently, knockdown of Znf219 decreased the Sox9-induced mRNA expression of these genes. Furthermore, a dominant-negative mutant Znf219 inhibited Bmp2-induced chondrocyte differentiation. Our results suggest that Znf219 plays an important role in the regulation of chondrocyte differentiation as a transcriptional partner of Sox9.

Links

PubMed Online version:10.1242/jcs.071373

Keywords

Animals; Bone Morphogenetic Protein 2/metabolism; Cell Differentiation/genetics; Cell Line; Cell Nucleus/metabolism; Chondrocytes/metabolism; Chondrocytes/pathology; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Extremities/growth & development; Gene Library; Genetic Testing; Humans; Mice; Mutation/genetics; Protein Binding; SOX9 Transcription Factor/genetics; SOX9 Transcription Factor/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transcriptional Activation

Significance

Annotations

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

MOUSE:CO2A1

involved_in

GO:0060174: limb bud formation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX6

involved_in

GO:0032332: positive regulation of chondrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q6IQX8

F

Seeded From UniProt

complete

MOUSE:SOX9

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SOX9

involved_in

GO:0032332: positive regulation of chondrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX9

involved_in

GO:0060174: limb bud formation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX9

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ZN219

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q04887

F

Seeded From UniProt

complete

MOUSE:ZN219

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ZN219

involved_in

GO:0032332: positive regulation of chondrocyte differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ZN219

involved_in

GO:0060174: limb bud formation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ZN219

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOX5

involved_in

GO:0032332: positive regulation of chondrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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