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Human ZNF312b oncogene is regulated by Sp1 binding to its promoter region through DNA demethylation and histone acetylation in gastric cancer

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Author(s)
In-Sung SongGa-Hee HaJeong-Min KimSo-Young JeongHan-Chul LeeYong Sung KimYung-Jin KimTaeg Kyu KwonNam-Soon Kim
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Institute for Medical Science (의과학연구소)
Journal Title
International Journal of Cancer
Issued Date
2011
Volume
129
Issue
9
Abstract
In a previous study, human ZNF312b was identified as a cell proliferation-associated oncogene via the K-ras/extracellular
signal-regulated kinase cascade in gastric cancer. However, the mechanism concerning its transcriptional activation remains
unknown. Here, we show that DNA methylation and histone acetylation of the ZNF312b promoter function as a switch for
ZNF312b transcriptional activation in gastric cancer. The transcription level of ZNF312b was increased by treatment with a
demethylating agent, 5-aza-2
0
-deoxycytidine and the histone deacetylase inhibitor sodium butyrate, in several human cancer
cell lines including gastric cancer. Consistent with these results, epigenetic analysis, such as pyrosequencing, bisulfate
sequencing and methyl-specific polymerase chain reaction (MSP), showed that the expression level of ZNF312b is highly
dependent on the degree of DNA methylation in gastric cancer cell lines. In addition, by ChIP assay using anti-acetyl/methyl
H3K9 antibodies, histone acetylation was shown to mediate the expression of the ZNF312b gene. Interestingly, ChIP assay
using the Sp1 antibody revealed that the binding of transcription factor Sp1 to the ZNF312b promoter for its transcriptional
activation requires DNA demethylation and histone acetylation. Moreover, a knockdown of Sp1 resulted in a decrease in ERK-
mediated proliferation via downregulation of the ZNF312b gene in gastric cancer cells. Taken together, these results suggest
that the aberrant expression of ZNF312b promotes gastric tumorigenesis through epigenetic modification of its promoter
region and provides a molecular mechanism for ZNF312b expression to contribute to the progression of gastric cancer.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
In-Sung Song et al. (2011). Human ZNF312b oncogene is regulated by Sp1 binding to its
promoter region through DNA demethylation and histone
acetylation in gastric cancer. International Journal of Cancer, 129(9), 2124–2133. doi: 10.1002/ijc.25871
Type
Article
ISSN
0020-7136
Source
https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.25871
DOI
10.1002/ijc.25871
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35966
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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