Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10.
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.
Kim
Joanna
J
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Shin
Sook
S
Subramaniam
Malayannan
M
Bruinsma
Elizabeth
E
Kim
Tae-Dong
TD
Hawse
John R
JR
Spelsberg
Thomas C
TC
Janknecht
Ralf
R
D002460:Cell Line; D051765:Early Growth Response Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human