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Nuclear factor Y (NF-Y) regulates the proximal promoter activity of the mouse collagen α1(XI) gene (Col11a1) in chondrocytes

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Abstract

Type XI collagen, a heterotrimer composed of α1(XI), α2(XI), and α3(XI), plays a critical role in cartilage formation and in skeletal morphogenesis. However, the transcriptional regulation of α1(XI) collagen gene (Col11a1) in chondrocyte is poorly characterized. In this study, we investigated the proximal promoter of mouse Col11a1 gene in chondrocytes. Major transcription start site was located at −299 bp upstream of the translation start site, and the proximal promoter lacks a TATA sequence but has a high guanine–cytosine (GC) content. Cell transfection experiments demonstrated that the segment from −116 to −256 is necessary for activation of the proximal Col11a1 promoter, and an electrophoretic mobility shift assay showed that a nuclear protein is bound to the segment from −116 to −176 in this promoter. Additional comparative and in silico analyses demonstrated that an ATTGG sequence, which is critical for binding to nuclear factor Y (NF-Y), is within the highly conserved region from −135 to −145. Interference assays using wild-type and mutant oligonucleotide or with specific antibody revealed that NF-Y protein is bound to this region. Cell transfection experiments with reporter constructs in the absence of NF-Y binding sequence exhibited the suppression of the promoter activity. Furthermore, chromatin immunoprecipitation assay demonstrated that NF-Y protein is directly bound to this region in vivo, and overexpression of dominant-negative NF-Y A mutant also inhibited the proximal promoter activity. Taken together, these results indicate that the transcription factor NF-Y regulates the proximal promoter activity of mouse Col11a1 gene in chondrocytes.

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Acknowledgments

We thank Ms. S. Adachi for the technical support and the staff members of Research Promotion Institute, Oita University. This work was supported by Grants-In-Aid for Scientific Research (no. 21591952 to N.M.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Matrix Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan

    Mariko Hida, Kouhei Yamashita, Takako Sasaki, Hidekatsu Yoshioka & Noritaka Matsuo

  2. Department of Cell Biology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan

    Ryoji Hamanaka

  3. Department of Dermatology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan

    Osamu Okamoto

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  1. Mariko Hida
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Correspondence to Noritaka Matsuo.

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Hida, M., Hamanaka, R., Okamoto, O. et al. Nuclear factor Y (NF-Y) regulates the proximal promoter activity of the mouse collagen α1(XI) gene (Col11a1) in chondrocytes. In Vitro Cell.Dev.Biol.-Animal 50, 358–366 (2014). https://doi.org/10.1007/s11626-013-9692-3

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