Identification of transcription factor AML-1 binding site upstream of human cytomegalovirus UL111A gene

Xiaoqun Zheng; Yan Gao; Qi Zhang; Yanqing Liu; Ying Peng; Miao Fu; Yanhong Ji

doi:10.1371/journal.pone.0117773

Identification of transcription factor AML-1 binding site upstream of human cytomegalovirus UL111A gene

PLoS One. 2015 Feb 6;10(2):e0117773. doi: 10.1371/journal.pone.0117773. eCollection 2015.

Authors

Xiaoqun Zheng¹, Yan Gao², Qi Zhang³, Yanqing Liu³, Ying Peng⁴, Miao Fu⁵, Yanhong Ji⁶

Affiliations

¹ Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Department of Laboratory Medicine, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Education Ministry of China, Wenzhou, Zhejiang, China.
² The First People's Hospital of Changde, Changde, Hunan, China.
³ Department of Laboratory Medicine, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Education Ministry of China, Wenzhou, Zhejiang, China.
⁴ School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Laboratory Medicine, Education Ministry of China, Wenzhou, Zhejiang, China.
⁵ Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China.
⁶ Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Abstract

Human cytomegalovirus (HCMV) interleukin-10 (hcmvIL-10), encoded by HCMV UL111A gene, is a homolog of human IL-10. It exerts immunomodulatory effects that allow HCMV to evade host defense mechanisms. However, the exact mechanism underlying the regulation of hcmvIL-10 expression is not well understood. The transcription factor acute myeloid leukemia 1 (AML-1) plays an important role in the regulation of various genes involved in the differentiation of hematopoietic lineages. A putative AML-1 binding site is present within the upstream regulatory region (URR) of UL111A gene. To provide evidence that AML-1 is involved in regulating UL111A gene expression, we examined the interaction of AML-1 with the URR of UL111A in HCMV-infected human monocytic THP-1 cells using a chromatin immunoprecipitation assay. HcmvIL-10 transcription was detected in differentiated THP-1 cells, but not in undifferentiated ones. Furthermore, the URR of UL111A showed a higher intensity of AML-1 binding, a higher level of histone H3 acetyl-K9, but a lower level of histone H3 dimethyl-K9 in differentiated THP-1 cells than undifferentiated cells. Down-regulation of AML1 by RNA interference decreased the expression of the UL111A gene. Our results suggest that AML-1 may contribute to the epigenetic regulation of UL111A gene via histone modification in HCMV-infected differentiated THP-1 cells. This finding could be useful for the development of new anti-viral therapies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Cell Line
Core Binding Factor Alpha 2 Subunit / genetics
Core Binding Factor Alpha 2 Subunit / metabolism*
Cytomegalovirus / genetics*
Down-Regulation
Epigenesis, Genetic
Gene Expression Regulation, Viral*
Histones / metabolism
Humans
Promoter Regions, Genetic

Substances

Core Binding Factor Alpha 2 Subunit
Histones
RUNX1 protein, human

Grants and funding

This study was supported by Chinese National Science Foundation Grant (NSFC) 81071365 (URL: http://isisn.nsfc.gov.cn/egrantindex/funcindex/prjsearch-list), and Zhejiang Provincial Natural Science Foundation Grant (ZJSFC) LY13H190006 (URL: http://www.zjnsf.gov.cn/1/xm/lx.aspx). Xiao-Qun Zheng received those two grants, and designed the project. In addition, both NSFC and ZJSFC also contributed to design this project.