상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Epigenetic modification of TLR4 promotes activation of NF-κB by regulating methyl-CpG-binding domain protein 2 and Sp1 in gastric cancer

Authors 

Tae Woo KimSeon-Jin LeeByung Moo OhHeesoo LeeTae Gi EomJeong Ki MinYoung-Jun ParkSuk Ran YoonBo Yeon KimJ W KimYong Kyung ChoeHee Gu Lee

Publisher 

Impact Journals

Issue Date 

2016

Citation 

Oncotarget, vol. 7, no. 4, pp. 4195-4209

Keywords 

Gastric cancerMethyl-CpG-binding domain protein 2MethylationSp1Toll-like receptor 4

Abstract 

Toll-like receptor 4 (TLR4) is important in promoting the immune response in various cancers. Recently, TLR4 is highly expressed in a stage-dependent manner in gastric cancer, but the regulatory mechanism of TLR4 expression has been not elucidated it. Here, we investigated the mechanism underlying regulation of TLR4 expression through promoter methylation and histone modification between transcriptional regulation and silencing of the TLR4 gene in gastric cancer cells. Chromatin immunoprecipitation was carried out to screen for factors related to TLR4 methylation such as MeCP2, HDAC1, and Sp1 on the TLR4 promoter. Moreover, DNA methyltransferase inhibitor 5-aza-deoxycytidine (5-aza-dC) induced demethylation of the TLR4 promoter and increased H3K4 trimethylation and Sp1 binding to reactivate silenced TLR4. In contrast, although the silence of TLR4 activated H3K9 trimethylation and MeCP2 complex, combined treatment with TLR4 agonist and 5-aza-dC upregulated H3K4 trimethylation and activated with transcription factors as Sp1 and NF-κB. This study demonstrates that recruitment of the MeCP2/HDAC1 repressor complex increases the low levels of TLR4 expression through epigenetic modification of DNA and histones on the TLR4 promoter, but Sp1 activates TLR4 high expression by hypomethylation and NF-κB signaling in gastric cancer cells.

ISSN 

1949-2553

Link 

http://dx.doi.org/10.18632/oncotarget.6549

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


Files in This Item: SizeFormat
13839.pdf4052KbAdobe PDF
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)