The mouse col11a2 gene. Some transcripts from the adjacent rxr-β gene extend into the col11a2 gene

doi:10.1016/S0945-053X(96)90139-0

Matrix Biology

Volume 15, Issue 5, November 1996, Pages 359-367

https://doi.org/10.1016/S0945-053X(96)90139-0 Get rights and content

Abstract

Type XI collagen is present in small amounts in cartilage, together with small amounts of type IX and type V collagens and large amounts of type II collagen. Here, primers based on the nucleotide sequences of partial human cDNAs and mouse genomic DNAs that were analyzed by other investigators were used to isolate a cDNA for the mouse of col11a2 gene. Cosmid clones for the mouse col11a2 gene were isolated, and 12.4 kb of the nucleotide sequences were defined. Analysis of the genomic sequences identified three exons in the mouse gene that were recently shown to undergo alternative splicing (Tsumaki and Kimura, J. Biol. Chem. 270, 2372–2378, 1995; Zhidkova et al., J. Biol. Chem., 270, 94886-9493, 1995). In addition, analysis of the cosmid clones revealed tht the 5′ end of the mouse col11a2 gene was located head-to-tail with the mouse retinoic X receptor β gene, RT-PCR assays demonstrated that some transcripts from the retinoic X receptor β gene extend into the col11a2 gene. Therefore, there may be coordinate expression of the two genes.

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Cited by (11)

The transcription factor CCAAT-binding factor CBF/NF-Y regulates the proximal promoter activity in the human α1(XI) collagen gene (COL11A1)
2003, Journal of Biological Chemistry
Citation Excerpt :
These observations in major fibrillar groups suggest that the mechanisms for basal transcriptional regulation of types II and III collagen may be distinct from those of type I collagen genes in regard to CBF/NF-Y. In the case of type XI collagen genes, previous studies indicated that the structure of the proximal promoter regions in the α1(XI) and α2(XI) genes exhibited the features of housekeeping genes, which have several GC boxes and no TATA box (17, 35–37). Our results first demonstrated that a functional CCAAT box exists in COL11A1 gene by directly binding to the proximal promoter region, whereas the 5′ flanking region of COL11A2 has no CCAAT box.
We have characterized the proximal promoter region of the human COL11A1 gene. Transient transfection assays indicate that the segment from –199 to +1 is necessary for the activation of basal transcription. Electrophoretic mobility shift assays (EMSAs) demonstrated that the ATTGG sequence, within the –147 to –121 fragment, is critical to bind nuclear proteins in the proximal COL11A1 promoter. We demonstrated that the CCAAT binding factor (CBF/NF-Y) bound to this region using an interference assay with consensus oligonucleotides and a supershift assay with specific antibodies in an EMSA. In a chromatin immunoprecipitation assay and EMSA using DNA-affinity-purified proteins, CBF/NF-Y proteins directly bound this region in vitro and in vivo. We also showed that four tandem copies of the CBF/NF-Y-binding fragment produced higher transcriptional activity than one or two copies, whereas the absence of a CBF/NF-Y-binding fragment suppressed the COL11A1 promoter activity. Furthermore, overexpression of a dominant-negative CBF-B/NF-YA subunit significantly inhibited promoter activity in both transient and stable cells. These results indicate that the CBF/NF-Y proteins regulate the transcription of COL11A1 by directly binding to the ATTGG sequence in the proximal promoter region.
More knee joint osteoarthritis (OA) in mice after inactivation of one allele of type II procollagen gene but less OA after lifelong voluntary wheel running exercise
2001, Osteoarthritis and Cartilage
Objective To investigate the incidence and severity of osteoarthritis (OA) and the effects of voluntary wheel running in normal mice and mice carrying either a targeted inactivation of one allele, heterozygous ‘knockout’, of Col2a1 gene or both alleles, homozygous ‘knockout’, of Col11a2 gene.
Methods Mice lived until 15 months of age in individual cages. Running activity was recorded around the clock. OA changes were evaluated from serial knee joint sections by light microscopy.
Results Heterozygous inactivation of Col2a1 gene coding for type II procollagen made the cartilage more susceptible to OA. At 15 months of age, OA prevalence was 60–90% in knockouts and 20–45% in normal controls (P< 0.01–0.001). Unexpectedly, a reduction of OA due to wheel running was observed in both knockout strains (P< 0.05–0.01). This effect was most evident in the femoral condyles. Incidence of OA in runners was approximately 50–85% of that in sedentary littermates. OA prevalence was higher in normal control and runner mice with high body weight. Running did not affect OA development in normal mice.
Conclusion Heterozygous knockout of Col2a1 gene increased the OA prevalence in mice. Lifelong voluntary wheel running had a protective effect against OA in both knockout mice lines. The reason for this remains unknown. Reduction of OA may result from the reorganization and strengthening of the articular cartilage collagen network and/or adjacent muscles due to running, or lower body weight. Increased compliance of the articular cartilage and bones of the knockout mice may also contribute to the reduction of OA in exercised animals.
Gene organisation, sequence variation and isochore structure at the centromeric boundary of the human MHC
1999, Journal of Molecular Biology
We have mapped and sequenced the region immediately centromeric of the human major histocompatibility complex (MHC). A cluster of 13 genes/pseudogenes was identified in a 175 kb PAC linking the TAPASIN locus with the class II region. It includes two novel human genes (BING4 and SACM2L) and a thus far unnoticed human leucocyte antigen (HLA) class II pseudogene, termed HLA-DPA3. Analysis of the G+C content revealed an isochore boundary which, together with the previously reported telomeric boundary, defines the MHC class II region as one of the first completely sequenced isochores in the human genome. Comparison of the sequence with limited sequence from other cell lines shows that the high sequence variation found within the classical class II region extends beyond the identified isochore boundary leading us to propose the concept of an “extended MHC”. By comparative analysis, we have precisely identified the mouse/human synteny breakpoint at the centromeric end of the extended MHC class II region between the genes HSET and PHF1.
A 1064 bp fragment from the promoter region of the Col11a2 gene drives lacZ expression not only in cartilage but also in osteoblasts adjacent to regions undergoing both endochondral and intramembranous ossification in mouse embryos
1998, Matrix Biology
We isolated a 1,064 bp promoter fragment that extended from the 3′-end of the adjacent gene for retinoic X receptor-β to beyond the most clearly defined start site of the mouse Col11a2 gene. The fragment was then joined to a β-galactosidase gene and used to prepare transgenic mice. Three independent lines of transgenic mice was generated. The reporter β-galactosidae gene was expressed in essentially all catilaginous tissues in 15.5-day-old mouse embyos. In additon, the construct was expressed in osteoprogenitors within developing periosteum and in osteoblasts within mineralized bone. This pattern of expression was evident during both endochondral and intramembranous bone formation. Therefore, the results suggest that 1,064 bp promoter fragment can drive tissue-specific expression of the Col11a2 gene.
Sp1 family of transcription factors regulates the human α2 (XI) collagen gene (COL11A2) in Saos-2 osteoblastic cells
2006, Journal of Bone and Mineral Research
Effect of retinoic acid on murine preosteoblastic MC3T3-E1 cells
2005, Journal of Nutritional Science and Vitaminology

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¹: Present Address: Center for Gene Therapy, Allegheny University for the Health Sciences, Mail Stop 421, 245 North 15th Street, Philadelphia, PA 19102

^∗: Dr. Darwin J. Prockop, Center for Gene Therapy, Allegheny University for the Health Sciences, Mail Stop 421, 15th and Vine Streets, Philadelphia, PA 19102

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Regular paperThe mouse col11a2 gene. Some transcripts from the adjacent rxr-β gene extend into the col11a2 gene

Abstract

Genomics

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

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Semin. Arth. Rheum.

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Genomics

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Regular paper
The mouse col11a2 gene. Some transcripts from the adjacent rxr-β gene extend into the col11a2 gene