Transcriptional repression by the basic helix-loop-helix protein Dec2: Multiple mechanisms through E-box elements

  • Authors:
    • Katsumi Fujimoto
    • Hidenori Hamaguchi
    • Takafumi Hashiba
    • Tadahiro Nakamura
    • Takeshi Kawamoto
    • Fuyuki Sato
    • Mitsuhide Noshiro
    • Ujjal K. Bhawal
    • Ketut Suardita
    • Yukio Kato
  • View Affiliations

  • Published online on: June 1, 2007     https://doi.org/10.3892/ijmm.19.6.925
  • Pages: 925-932
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Abstract

Dec2, a member of the basic helix-loop-helix (bHLH) superfamily, has been shown to function as a transcriptional repressor and is implicated in cell proliferation and differentiation. In addition, Dec2 transcripts exhibit a striking circadian oscillation in the suprachiasmatic nucleus. To identify the molecular mechanisms by which Dec2 regulates gene expression, we carried out structure-function analyses. Gel retardation and luciferase assays showed that Dec2, as well as its related protein Dec1, preferentially binds to class B E-box elements (CACGTG) as a homodimer and represses the transcription of target genes in a histone deacetylase (HDAC)-dependent manner. Functional studies with the GAL4-DNA binding domain fusion proteins identified the domain responsible for the repression activity of Dec2 in its C-terminal region, which is also necessary to recruit HDAC1. In addition, the basic and HLH domains of Dec2 were required for DNA binding and homodimerization, respectively. In contrast, Dec proteins repressed a MyoD-activated promoter activity of muscle creatine kinase gene through class A E-box in an HDAC1-independent manner. Dec2 formed a heterodimer with MyoD through the basic and HLH domains. Consistent with this, both the basic and HLH domains were required for the ability of Dec2 to inhibit the transcriptional activity of MyoD. These findings indicate that Dec2 employs multiple mechanisms, including DNA-binding and protein-protein interactions, to achieve E-box-dependent transcriptional repressions.

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June 2007
Volume 19 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Fujimoto K, Hamaguchi H, Hashiba T, Nakamura T, Kawamoto T, Sato F, Noshiro M, Bhawal UK, Suardita K, Kato Y, Kato Y, et al: Transcriptional repression by the basic helix-loop-helix protein Dec2: Multiple mechanisms through E-box elements. Int J Mol Med 19: 925-932, 2007
APA
Fujimoto, K., Hamaguchi, H., Hashiba, T., Nakamura, T., Kawamoto, T., Sato, F. ... Kato, Y. (2007). Transcriptional repression by the basic helix-loop-helix protein Dec2: Multiple mechanisms through E-box elements. International Journal of Molecular Medicine, 19, 925-932. https://doi.org/10.3892/ijmm.19.6.925
MLA
Fujimoto, K., Hamaguchi, H., Hashiba, T., Nakamura, T., Kawamoto, T., Sato, F., Noshiro, M., Bhawal, U. K., Suardita, K., Kato, Y."Transcriptional repression by the basic helix-loop-helix protein Dec2: Multiple mechanisms through E-box elements". International Journal of Molecular Medicine 19.6 (2007): 925-932.
Chicago
Fujimoto, K., Hamaguchi, H., Hashiba, T., Nakamura, T., Kawamoto, T., Sato, F., Noshiro, M., Bhawal, U. K., Suardita, K., Kato, Y."Transcriptional repression by the basic helix-loop-helix protein Dec2: Multiple mechanisms through E-box elements". International Journal of Molecular Medicine 19, no. 6 (2007): 925-932. https://doi.org/10.3892/ijmm.19.6.925