Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10

Joanna Kim, Sook Shin, Malayannan Subramaniam, Elizabeth Bruinsma, Tae Dong Kim, John R. Hawse, Thomas C. Spelsberg, Ralf Janknecht

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

JARID1B/KDM5B (jumonji AT-rich interactive domain 1B/lysine-specific demethylase 5B) is an enzyme that efficiently removes methyl residues from trimethylated lysine 4 on histone H3, a pivotal mark for active chromatin. TIEG1/KLF10 (transforming growth factor-β inducible early gene-1/Krüppel-like transcription factor 10) is a zinc-finger transcription factor that is involved in bone metabolism and exerts antiproliferative activity. Here, we found that TIEG1 interacts with JARID1B. In particular, the repression domains of TIEG1 bind to the C-terminus of JARID1B. Moreover, overexpression of JARID1B augments TIEG1 to repress transcription of Smad7, an inhibitor of the TGF-β (transforming growth factor-β) signaling pathway. Conversely, JARID1B knock-down leads to increased Smad7 mRNA levels. Thus, TIEG1 and JARID1B may cooperate to suppress tumorigenesis by enhancing TGF-β signaling. Notably, both TIEG1 and JARID1B are downregulated in melanomas, suggesting that they indeed cooperate physiologically. In conclusion, JARID1B is the first TIEG1 corepressor identified, explaining how TIEG1 represses transcription through inducing histone H3 lysine 4 demethylation, which may be important for TIEG1 function in both normal and cancer cells.

Original languageEnglish (US)
Pages (from-to)412-416
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume401
Issue number3
DOIs
StatePublished - Oct 22 2010

Keywords

  • Cancer
  • Corepressor
  • Histone demethylase
  • Krüppel-like transcription factor
  • Smad7
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10'. Together they form a unique fingerprint.

  • Cite this

    Kim, J., Shin, S., Subramaniam, M., Bruinsma, E., Kim, T. D., Hawse, J. R., Spelsberg, T. C., & Janknecht, R. (2010). Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10. Biochemical and Biophysical Research Communications, 401(3), 412-416. https://doi.org/10.1016/j.bbrc.2010.09.068