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Identification of a novel bone morphogenetic protein (BMP)-inducible transcript, BMP-inducible transcript-1, by utilizing the conserved BMP-responsive elements in the Id genes

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Abstract

Bone morphogenetic proteins (BMPs) inhibit myogenesis and induce osteoblastic differentiation in myoblasts. They also induce the transcription of several common genes, such as Id1, Id2 and Id3, in various cell types. We have reported that a GC-rich element in the Id1 gene functions as a BMP-responsive element (BRE) that is regulated by Smads. In this study, we analyzed and identified BREs in the 5′-flanking regions of the mouse Id2 and Id3 genes. The core GGCGCC sequence was conserved among the BREs in the Id1, Id2 and Id3 genes and was essential for the response to BMP signaling via Smads. We found a novel BRE on mouse chromosome 13 at position 47,723,740–47,723,768 by searching for conserved sequences containing the Id1 BRE. This potential BRE was found in the 5′-flanking region of a novel gene that produces a non-coding transcript, termed BMP-inducible transcript-1 (BIT-1), and this element regulated the expression of this gene in response to BMP signaling. We found that BIT-1 is expressed in BMP target tissues such as the testis, brain, kidney and cartilage. These findings suggest that the transcriptional induction of the Ids, BIT-1 and additional novel genes containing the conserved BRE sequence may play an important role in the regulation of the differentiation and/or function of target cells in response to BMPs.

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Acknowledgments

This work was supported in part by Health and Labour Sciences Research Grants for Research on Measures for Intractable Research from the Ministry of Health, Labour and Welfare of Japan, grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, a grant-in-aid for the Supported Program for the Strategic Research Foundation at Private Universities from the MEXT (S0801004) and a grant-in-aid from the Takeda Science Foundation.

Conflict of interest

All authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama, 350-1241, Japan

    Masashi Shin, Satoshi Ohte, Toru Fukuda, Hiroki Sasanuma, Katsumi Yoneyama, Shoichiro Kokabu, Arei Miyamoto, Sho Tsukamoto & Takenobu Katagiri

  2. Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, 187-8502, Japan

    Hirohiko Hohjoh

  3. Department of Biosciences, Kyushu Dental College, Kitakyushu-shi, Fukuoka, 803-8580, Japan

    Eijiro Jimi

Authors
  1. Masashi Shin
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  2. Satoshi Ohte
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  3. Toru Fukuda
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  4. Hiroki Sasanuma
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  5. Katsumi Yoneyama
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  6. Shoichiro Kokabu
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  7. Arei Miyamoto
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  8. Sho Tsukamoto
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  9. Hirohiko Hohjoh
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  10. Eijiro Jimi
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  11. Takenobu Katagiri
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Correspondence to Takenobu Katagiri.

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Shin, M., Ohte, S., Fukuda, T. et al. Identification of a novel bone morphogenetic protein (BMP)-inducible transcript, BMP-inducible transcript-1, by utilizing the conserved BMP-responsive elements in the Id genes. J Bone Miner Metab 31, 34–43 (2013). https://doi.org/10.1007/s00774-012-0381-1

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  • DOI: https://doi.org/10.1007/s00774-012-0381-1

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