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PMID:21346191

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Citation

Amano, K, Hata, K, Muramatsu, S, Wakabayashi, M, Takigawa, Y, Ono, K, Nakanishi, M, Takashima, R, Kogo, M, Matsuda, A, Nishimura, R and Yoneda, T (2011) Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription. Mol. Biol. Cell 22:1300-11

Abstract

SRY-box-containing gene 9 (Sox9) is an essential transcription factor in chondrocyte lineage determination and differentiation. Recent studies demonstrated that Sox9 controls the transcription of chondrocyte-specific genes in association with several other transcriptional regulators. To further understand the molecular mechanisms by which Sox9 influences transcriptional events during chondrocyte differentiation, we attempted to identify transcriptional partners of Sox9 and to examine their roles in chondrocyte differentiation. We isolated AT-rich interactive domain-containing protein 5a (Arid5a; also known as Mrf1) as an activator of the Col2a1 gene promoter from an ATDC5 cDNA library. Arid5a was highly expressed in cartilage and induced during chondrocyte differentiation. Furthermore, Arid5a physically interacted with Sox9 in nuclei and up-regulated the chondrocyte-specific action of Sox9. Overexpression of Arid5a stimulated chondrocyte differentiation in vitro and in an organ culture system. In contrast, Arid5a knockdown inhibited Col2a1 expression in chondrocytes. In addition, Arid5a binds directly to the promoter region of the Col2a1 gene and stimulates acetylation of histone 3 in the region. Our results suggest that Arid5a may directly interact with Sox9 and thereby enhance its chondrocyte-specific action.

Links

PubMed PMC3078073 Online version:10.1091/mbc.E10-07-0566

Keywords

Adenoviridae; Animals; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cartilage/embryology; Cartilage/metabolism; Cell Differentiation/genetics; Cell Line; Cell Proliferation; Chondrocytes/cytology; Chondrocytes/metabolism; Chondrogenesis/genetics; Collagen Type II/genetics; Collagen Type II/metabolism; Embryo, Mammalian/metabolism; Escherichia coli; Female; Gene Expression; Gene Library; Luciferases, Firefly/analysis; Mice; Organ Culture Techniques; Plasmids; Promoter Regions, Genetic; Protein Binding/genetics; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; SOX9 Transcription Factor/genetics; SOX9 Transcription Factor/metabolism; Transcriptional Activation

Significance

Annotations

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

HUMAN:SOX9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3U108

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

part_of

GO:0005667: transcription regulator complex

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3U108

C

Seeded From UniProt

complete

MOUSE:SOX9

acts_upstream_of_or_within

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

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:2443039

P

Seeded From UniProt

complete

MOUSE:ARI5A

acts_upstream_of_or_within

GO:0002062: chondrocyte differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ARI5A

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ARI5A

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:ARI5A

part_of

GO:0005667: transcription regulator complex

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q04887

C

Seeded From UniProt

complete

MOUSE:ARI5A

acts_upstream_of_or_within

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

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98371

P

Seeded From UniProt

complete

MOUSE:ARI5A

acts_upstream_of_or_within

GO:0035066: positive regulation of histone acetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ARI5A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P48436

F

Seeded From UniProt

complete


See also

References

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