TY - JOUR
T1 - Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10
AU - Kim, Joanna
AU - Shin, Sook
AU - Subramaniam, Malayannan
AU - Bruinsma, Elizabeth
AU - Kim, Tae Dong
AU - Hawse, John R.
AU - Spelsberg, Thomas C.
AU - Janknecht, Ralf
N1 - Funding Information:
This work was generously supported by the Bruce and Martha Atwater Foundation and NIH Grant R01DE014036 . These funding sources had no role in the study design, data collection, data interpretation, writing of this report, and the decision to submit this paper for publication.
PY - 2010/10/22
Y1 - 2010/10/22
N2 - 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.
AB - 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.
KW - Cancer
KW - Corepressor
KW - Histone demethylase
KW - Krüppel-like transcription factor
KW - Smad7
KW - Transforming growth factor-β
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U2 - 10.1016/j.bbrc.2010.09.068
DO - 10.1016/j.bbrc.2010.09.068
M3 - Article
C2 - 20863814
AN - SCOPUS:77958150187
SN - 0006-291X
VL - 401
SP - 412
EP - 416
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -