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Journal of Systems Biology & Proteome Research | Volume 2
J u n e 2 5 - 2 7 , 2 0 1 8 | D u b l i n , I r e l a n d
MASS SPECTROMETRY
AND PROTEOMICS
International Conference on
Jianjun Liu et al., J Syst Biol Proteome Res 2018, Volume 2
DOWN-REGULATION OF P53 BY SET
CONTRIBUTES TO TCE-INDUCED DNA
DAMAGE THROUGH INHIBITION OF
H3K79 DI-METHYLATION
Jianjun Liu, Xiaohu Ren, Zhihong Chen, Jiawen Ruan and
Nuanyuan luo
Shenzhen Center for Disease Control and Prevention, China
Trichloroethylene (TCE) is an occupational and environmental chemical
that can cause severe hepatotoxicity. Previously we have observed in a
model of TCE-induced apoptosis of cultured human hepatocytes (L-02 cell
line) that SET (a protein encoded by the SET gene in humans) is abnormally
elevated which acts as a key mediator in TCE-induced hepatic cytotoxicity, but
the underlying mechanisms still remain elusive. In this study，we found that
TCE induced DNA damage in liver cells using comet assay. Additionally, SET
related histone methylation were analyzed using the combination of triton-
acid-urea polyacrylamide gel electrophoresis (TAU-SDS-PAGE) and LC-MS/
MS. 22 SET-mediated abnormally altered histone methylation were identified
and the H3K79 di-methylation (H3K79me2), which was related with DNA
damage and gene transcription, was validated by Western-blot analysis. We
revealed that SET inhibited H3K79 di-methylation within the promoter region
of p53 under the treatment of TCE by using chromatin immunoprecipitation-
quantitative PCR (CHIP-qPCR) analysis. Further inhibition of H3K79 specific
methyltransferase DOT1L verified that SET-mediated decreasing H3K79 di-
methylation caused down-regulation of p53 and aggregated DNA damage.
These findings indicate that SET aggregates TCE-induced DNA damage
through partially blocking the repair process via dysregulation of p53.
Jianjun Liu has completed her M.D. in 1989
from University of Xiangtan, and now, she is
post-doctor supervisor of Southern Medical
University. Her major research interests include
proteomic analysis and biomarker screening of
chemical pollutant-induced damage to human,
safety assessment of nano-materials, develop-
ment of testing techniques for food safety. She
has published more than 70 research papers.
Additionally, in the past five years, she has re-
ceived over ten grants, such as National Science
Foundation of China, the Guangdong Natural
Science Foundation, Sanming Project of Medi-
cine in Shenzhen, and so on.
BIOGRAPHY