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

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 understoo...

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Bibliographic Details
Published in:PloS one 2015-02, Vol.10 (2), p.e0117773-e0117773
Main Authors: Zheng, Xiaoqun, Gao, Yan, Zhang, Qi, Liu, Yanqing, Peng, Ying, Fu, Miao, Ji, Yanhong
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
AML1 protein
Antiviral agents
Binding Sites
Cell Line
Chemical properties
Chromatin
Core Binding Factor Alpha 2 Subunit - genetics
Core Binding Factor Alpha 2 Subunit - metabolism
Cytokines
Cytomegalovirus
Cytomegalovirus - genetics
DNA methylation
Down-Regulation
Education
Epigenesis, Genetic
Epigenetic inheritance
Gene expression
Gene Expression Regulation, Viral
Gene regulation
Genes
Histone H3
Histones - metabolism
Homology
Hospitals
Humans
Immunology
Immunomodulation
Immunoprecipitation
Infections
Interleukin 10
Interleukins
Laboratories
Leukemia
Medicine
Monocytes
Myeloid leukemia
Penicillin
Promoter Regions, Genetic
Ribonucleic acid
RNA
RNA-mediated interference
Transcription factors
Viral infections
Virology
Viruses
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0117773