Oncotarget

Research Papers:

Hepatitis B virus X protein influences enrichment profiles of H3K9me3 on promoter regions in human hepatoma cell lines

Di-Yi Wang, Shu-Hong An, Lei Liu, Shan-Shan Bai, Kai-Xiang Wu, Rong Zhu and Zhao-Jin Wang _

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Oncotarget. 2016; 7:84883-84892. https://doi.org/10.18632/oncotarget.12751

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Abstract

Di-Yi Wang1, Shu-Hong An2, Lei Liu1, Shan-Shan Bai3, Kai-Xiang Wu1, Rong Zhu4, Zhao-Jin Wang2

1Department of Pathology, Affiliated Hospital of Taishan Medical University, Taian 271000, China

2Department of Human Anatomy, Taishan Medical University, Taian, 271000, China

3Department of Pathology, The First people’s Hospital of Taian, Taian, 271000, China

4Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Correspondence to:

Zhao-Jin Wang, email: zjwang@tsmc.edu.cn

Keywords: hepatitis B virus X protein, histone H3 lysine 9 trimethylation, gene promoters, hepatocellular carcinoma

Received: May 10, 2016    Accepted: October 12, 2016    Published: October 19, 2016

ABSTRACT

We previously showed that hepatitis B virus (HBV) X protein (HBx) could promote the trimethylation of histone H3 lysine 9 (H3K9me3) to repress tumor suppressor genes in hepatocellular carcinoma (HCC). In this work, we analyze 23,148 human promoters using ChIP-chip to determine the effects of HBx on H3K9me3 enrichments in hepatoma cells with transfection of HBx-expressing plasmid. Immunohistochemistry for HBx and H3K9me3 was performed in 21 cases of HBV-associated HCC tissues. We identified that H3K9me3 immunoreactivity was significantly correlated with HBx staining in HCC tissues. ChIP-chip data indicated that HBx remarkably altered promoter enrichments of H3K9me3 in hepatoma cells. We identified 25 gene promoters, whose H3K9me3 enrichments are significantly altered in hepatoma cells transfected HBx-expressing plasmid, including 19 gaining H3K9m3, and six losing this mark. Most of these genes have not been previously reported in HCC, and BTBD17, MIR6089, ZNF205-AS1 and ZP1 have not previously been linked to cancer; only two genes (DAB2IP and ZNF185) have been reported in HCC. Genomic analyses suggested that genes with the differential H3K9me3 enrichments function in diverse cellular pathways and many are involved in cancer development and progression.


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