Crosstalk between transcriptional control and energy pathways, mediated by hub metabolites

Scientific Research on Innovative Areas, a MEXT Grant-in-Aid Project FY2011-2015

Yahagi Group: Exploring the mechanisms of metabolic control of gene expression through new approaches of nutrigenomics

Research Structure

Principal Investigator Naoya Yahagi Naoya Yahagi
Associate Professor,
Graduate School of Comprehensive Human Sciences
University of Tsukuba
Web: http://metab.umin.ne.jp/index-e.shtml
E-mail:

Summary

In the process of gene regulation, transcription factors serve as ‘eyes’ that read out specific DNA sequences in response to metabolic signals. In order to serve this purpose, transcription factors need to be localized at specific sites in the genome, and form complexes with multiple nuclear factors.

In collaboration with colleagues, the principal investigator has established a quantitative system that combines adenovirus-mediated transduction of luciferase reporter gene into the liver with in vivo imaging system (IVIS) technique (in vivo Ad-luc analytical system) to create an intra-organ assay system for the analysis of energy metabolism and metabolic signals. Moreover, we have developed the Transcription Factor Expression Library (TFEL), which covers all known transcription factors encoded by the mouse genome, and created a method for the analysis of transcription complexes using this library (TFEL scan method).

Here, we will employ our in vivo Ad-luc analytical method to identify the genomic regions acted upon by a range of signals related to energy metabolism. We will then apply the TFEL scan method to the regions we identify in order to explore the mechanisms underlying the metabolic control of gene expression through these new approaches of nutrigenomics.

Recent Publications 

  1. Izumida, Y., *Yahagi, N., Takeuchi ,Y., Nishi, M., Shikama, A., Takarada, A., Masuda, Y., Kubota, M., Matsuzaka, T., Nakagawa, Y., Iizuka, Y., Itaka, K., Kataoka, K., Shioda, S., Niijima, A., Yamada, T., Katagiri, H., Nagai, R., Yamada, N., Kadowaki, T., and Shimano H.
    Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization.
    Nature Commun. 4, Article number 2316 (2013)  pubmed
  2. Kumadaki, S., Karasawa, T., Matsuzaka, T., Ema, M., Nakagawa, Y., Nakakuki, M., Saito, R., Yahagi, N., Iwasaki, H., Sone, H., Takekoshi, K., Yatoh, S., Kobayashi, K., Takahashi, A., Suzuki, H., Takahashi, S., Yamada, N., and *Shimano, H.
    Inhibition of ubiquitin ligase F-box and WD repeat domain-containing 7α (Fbw7α) causes hepatosteatosis through Krüppel-like factor 5 (KLF5)/peroxisome proliferator-activated receptor γ2 (PPARγ2) pathway but not SREBP-1c protein in mice.
    J. Biol. Chem. 286, 40835-40846 (2011)    pubmed

Major Publications

  1. Takeuchi, Y., *Yahagi, N., Izumida, Y., Nishi, M., Kubota, M., Teraoka, Y., Yamamoto, T., Matsuzaka, T., Nakagawa, Y., Sekiya, M., Iizuka, Y., Ohashi, K., Osuga, JI., Gotoda, T., Ishibashi, S., Itaka, K., Kataoka, K., Nagai, R., Yamada, N., Kadowaki, T., and Shimano, H.
    Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit.
    J. Biol. Chem.     285, 11681-11691 (2010)
  2. Inoue, N., Yahagi, N., Yamamoto, T., Ishikawa, M., Watanabe, K., Matsuzaka, T., Nakagawa, Y., Takeuchi, Y., Kobayashi, K., Takahashi, A., Suzuki, H., Hasty, AH., Toyoshima, H., Yamada, N., and *Shimano, H.
    Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity and insulin resistance.
    J. Biol. Chem. 283, 21220-21229 (2008)
  3. Takeuchi, Y., Yahagi, N., Nakagawa, Y., Matsuzaka, T., Shimizu, R., Sekiya, M., Iizuka, Y., Ohashi, K., Gotoda, T., Yamamoto, M., Nagai, R., Kadowaki, T., Yamada, N., Osuga, JI., and *Shimano, H.
    In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression. Biochem. Biophys. Res. Commun. 363, 329-335 (2007)
  4. Sekiya, M., Yahagi, N., Matsuzaka, T., Takeuchi, Y., Nakagawa, Y., Takahashi, H., Okazaki, H., Iizuka, Y., Ohashi, K., Gotoda, T., Ishibashi, S., Nagai, R., Yamazaki, T., Kadowaki, T., Yamada, N., Osuga, JI., and *Shimano, H.
    Sterol regulatory element-binding protein (SREBP) -1-independent regulation of lipogenic gene expression in adipocytes.
    J. Lipid Res. 48,1581-1591 (2007)
  5. Matsuzaka, T., *Shimano, H., Yahagi, N., Kato, T., Atsumi, A., Yamamoto, T., Inoue, N., Ishikawa, M., Okada, S., Ishigaki, N., Iwasaki, H., Iwasaki, Y., Karasawa, T., Kumadaki, S., Matsui, T., Sekiya, M., Ohashi, K., Hasty, AH., Nakagawa, Y., Takahashi, A., Suzuki, H., Yatoh, S., Sone, H., Toyoshima, H., Osuga, JI., and Yamada, N.
    Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance.
    Nat. Med. 13, 1193-1202 (2007)
  6. Nakagawa, Y., Shimano, H., Yoshikawa, T., Ide, T., Tamura, M., Furusawa, M., Yamamoto, T., Inoue, N., Matsuzaka, T., Takahashi, A., Hasty, AH., Suzuki, H., Sone, H., Toyoshima, H., Yahagi, N., and Yamada, N.
    TFE3, a novel transcription factor for hepatic IRS-2 and insulin signals, ameliorates diabetes.
    Nat. Med. 12, 107-113 (2006)
  7. Najima, Y., Yahagi, N., Takeuchi, Y., Matsuzaka, T., Sekiya, M., Nakagawa, Y., Amemiya-Kudo, M., Okazaki, H., Okazaki, S., Tamura, Y., Iizuka, Y., Ohashi, K., Harada, K., Gotoda, T., Nagai, R., Kadowaki, T., Ishibashi, S., Yamada, N., Osuga, JI., and *Shimano, H.
    High mobility group protein-B1 (HMGB1) interacts with sterol regulatory element-binding proteins (SREBPs) to enhance their DNA binding.
    J. Biol. Chem. 280, 27523-27532 (2005)
  8. Ide, T., *Shimano, H., Yahagi, N., Matsuzaka, T., Nakakuki, M., Yamamoto, T., Nakagawa, Y., Takahashi, A., Suzuki, H., Sone, H., Toyoshima, H., Fukamizu, A., and Yamada, N.
    SREBPs suppress IRS-2-mediated insulin signalling in the liver.
    Nat. Cell Biol. 6, 351-357 (2004)
  9. Yahagi, N., *Shimano, H., Matsuzaka, T., Sekiya, M., Najima, Y., Okazaki, S., Okazaki, H., Tamura, Y., Iizuka, Y., Inoue, N., Nakagawa, Y., Takeuchi, Y., Ohashi, K., Harada, K., Gotoda, T., Nagai, R., Kadowaki, T., Ishibashi, S., Osuga, JI., and Yamada, N.
    p53 involvement in the pathogenesis of fatty liver disease.
    J. Biol. Chem. 279, 20571-20575 (2004)
  10. Yahagi, N., *Shimano, H., Matsuzaka, T., Najima, Y., Sekiya, M., Nakagawa, Y., Ide, T., Tomita, S., Okazaki, H., Tamura, Y., Iizuka, Y., Ohashi, K., Gotoda, T., Nagai, R., Kimura, S., Ishibashi, S., Osuga, JI., and Yamada, N.
    p53 activation in adipocytes of obese mice.
    J. Biol. Chem. 278, 25395-25400 (2003)

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