Regulation of Human COL9A1 Gene Expression

Zhang, Ping; Jimenez, Sergio A.; Stokes, David G.

doi:10.1074/jbc.m208049200

Cited by 111 publications

(37 citation statements)

References 32 publications

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“…This effect of L-SOX5 and SOX6 to SOX9 is not consistent among all cartilage matrix genes, however. For example, SOX9-mediated transcription from the COL9A1 promoter is not stimulated by L-SOX5 and SOX6 (19). In the pellet culture of hMSC and hDFB cells, we observed no additive effect of L-SOX5 and SOX6 to SOX9 activity, whereas SOX9 expression itself was sufficient for CRTL1 induction.…”

Section: Function Of the Sox9-dependent Enhancer Element In A Chondromentioning

confidence: 55%

SOX9-dependent and -independent Transcriptional Regulation of Human Cartilage Link Protein

Kou¹,

Ikegawa²

2004

Journal of Biological Chemistry

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Cartilage link protein is a key component of the cartilage extracellular matrix. The transcriptional regulation of the gene encoding cartilage link protein (CRTL1) is largely unknown, however. Here, we investigated the regulation of CRTL1 by SOX9, a key regulator of cartilage matrix genes and chondrogenesis. Knockdown of SOX9 resulted in decreased CRTL1 expression. SOX9 induced CRTL1 expression effectively in human nonchondrocytic immortalized cell lines as well as in mesenchymal stem cell and adult dermal fibroblast. These results indicate that, like other cartilage matrix genes, SOX9 is a key regulator of CRTL1. Unlike other cartilage matrix genes, however, the activation of CRTL1 by SOX9 and its known transcriptional co-activators L-SOX5 and SOX6 was cell type-dependent. Two cis-acting enhancer elements resided in the 5-untranslated region of CRTL1. One contained a heptameric SOX binding sequence and showed SOX9-dependent enhancer activity in several cell lines. The other showed cell type-specific SOX9-independent enhancer activity. These findings suggest that the enhancer elements may mediate differential expression of CRTL1 during chondrocyte differentiation and maturation.

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Section: Function Of the Sox9-dependent Enhancer Element In A Chondromentioning

confidence: 55%

SOX9-dependent and -independent Transcriptional Regulation of Human Cartilage Link Protein

Kou¹,

Ikegawa²

2004

Journal of Biological Chemistry

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“…3D). Some 3 -SOX9 with three different lysine-to-alanine mutations was cotransfected into COS-7 cells with GFP-PIAS1 and FLAG-SUMO-1. Equal amounts of total cell lysates were loaded on the gel, and wild-type or mutant HA 3 -SOX9 was detected with anti-HA monoclonal antibody.…”

Section: Pias1 -X␣ -X␤ and -3 Enhance Sox9-dependent Transactivatimentioning

confidence: 99%

“…Members of the SOX9 family of transcription factors contain a high mobility group (HMG) 3 box DNA-binding domain that is at least 50% identical to an equivalent domain in the sex-determining factor SRY (8). SOX9 also contains a potent transcriptional activation domain located at its C-terminal end.…”

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confidence: 99%

Interactions between PIAS Proteins and SOX9 Result in an Increase in the Cellular Concentrations of SOX9

Hattori

Eberspaecher

Lü

et al. 2006

Journal of Biological Chemistry

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We have identified PIAS1 (protein inhibitor of activated STAT-1), -3, -x␣, and -x␤ as SOX9-associated polypeptides using the Gal4-based yeast two-hybrid system and a cDNA library derived from a chondrocytic cell line. These PIAS proteins were shown to interact directly with SOX9 in two-hybrid, co-immunoprecipitation, and electrophoretic mobility shift assays. SOX9 was sumoylated in cotransfection experiments with COS-7 cells using PIAS and SUMO-1 (small ubiquitin-like modifier-1) expression vectors. SOX9 was also sumoylated in vitro by PIAS proteins in the presence of SUMO-1, the SUMOactivating enzyme, and the SUMO-conjugating enzyme. In COS-7 cells, PIAS proteins stimulated the SOX9-dependent transcriptional activity of a Col2a1 promoter-enhancer reporter. This increase in reporter activity was paralleled by an increase in the cellular levels of SOX9. Cotransfection with a SUMO-expressing vector further enhanced the transcriptional activity of this SOX9-dependent Col2a1 reporter in COS-7 cells, and this additional activation was inhibited in the presence of either SUMO-1 mutants or PIAS RING domain mutants or by coexpression of a desumoylation enzyme. Immunofluorescence microscopy of SOX9-transfected COS-7 cells showed that the subnuclear distribution of SOX9 became more diffuse in the presence of PIAS1 and SUMO-1. Our results suggest that, by controlling the cellular concentrations of SOX9, PIAS proteins and sumoylation may be part of a major regulatory system of SOX9 functions.SOX9, a transcription factor of the SRY (sex-determining region, Y chromosome) family, is required for the establishment and differentiation of several cell lineages, including those of chondrocytes, Sertoli cells of male gonads, glial cells of the nervous system, and others. During chondrocyte differentiation, SOX9 is expressed abundantly in mouse chondroprogenitor cells and overtly differentiated chondrocytes (1) and regulates transcription of cartilage-specific extracellular matrix molecules such as collagen types II (2), IX (3), and XI (4) and aggrecan (5). Heterozygous mutations in the Sox9 gene cause campomelic dysplasia, a severe skeletal malformation syndrome characterized by a generalized hypoplasia of endochondral bones. SOX9 inactivation studies in mice indicate that SOX9 has an essential role in several steps of chondrogenic differentiation, including mesenchymal condensations and overt differentiation of chondrocytes (1, 6). In the absence of SOX9, no chondrocyte marker genes are expressed (1), but the precise mechanism of transcriptional activation by SOX9 of cartilage-specific genes is only poorly understood. The cellular concentration of SOX9 must be tightly regulated in vivo given that campomelic dysplasia is due to haploinsufficiency of SOX9 and because a modest increase in SOX9 expression results in dwarfism in mice (7).Members of the SOX9 family of transcription factors contain a high mobility group (HMG) 3 box DNA-binding domain that is at least 50% identical to an equivalent domain in the sex-determining factor SRY...

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“…Members of the SOX family have been found to be responsible for the transcriptional regulation of type II and IX collagen genes including COL2A1 and COL9A1 (Bell et al 1997, Stokes et al 2001. Particularly, SOX9 played an important role in COL9A1 gene expression (Zhang et al 2003). Therefore, one can argue that via members of SOX family, TSH may be involved in the regulation of collagen synthesis during cartilage generation.…”

Section: Discussionmentioning

confidence: 99%

TSH-induced gene expression involves regulation of self-renewal and differentiation-related genes in human bone marrow-derived mesenchymal stem cells

Bagriacik

Yaman²,

Haznedar³

et al. 2011

Journal of Endocrinology

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Bone marrow-derived mesenchymal stem cells are pluripotent cells that are capable of differentiating into a variety of cell types including neuronal cells, osteoblasts, chondrocytes, myocytes, and adipocytes. Despite recent advances in stem cell biology, neuroendocrine relations, particularly TSH interactions remain elusive. In this study, we investigated expression and biological consequence of TSH receptor (TSHR) interactions in mesenchymal stem cells of cultured human bone marrow. To the best of our knowledge, we demonstrated for the first time that human bone marrow-derived mesenchymal stem cells expressed a functional thyrotropin receptor that was capable of transducing signals through cAMP. We extended this study to explore possible pathways that could be associated directly or indirectly with the TSHR function in mesenchymal stem cells. Expression of 80 genes was studied by real-time PCR array profiles. Our investigation indicated involvements of interactions between TSH and its receptor in novel regulatory pathways, which could be the important mediators of self-renewal, maintenance, development, and differentiation in bone marrow-derived mesenchymal stem cells. TSH enhanced differentiation to the chondrogenic cell lineage; however, further work is required to determine whether osteoblastic differentiation is also promoted. Our results presented in this study have opened an era of regulatory events associated with novel neuroendocrine interactions of hypothalamic-pituitary axis in mesenchymal stem cell biology and differentiation.

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Regulation of Human COL9A1 Gene Expression

Cited by 111 publications

References 32 publications

SOX9-dependent and -independent Transcriptional Regulation of Human Cartilage Link Protein

SOX9-dependent and -independent Transcriptional Regulation of Human Cartilage Link Protein

Interactions between PIAS Proteins and SOX9 Result in an Increase in the Cellular Concentrations of SOX9

TSH-induced gene expression involves regulation of self-renewal and differentiation-related genes in human bone marrow-derived mesenchymal stem cells

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