Epigenetic regulation of cytomegalovirus major immediate-early promoter activity in transgenic mice

The expression of genes in transgenic mice is known to be influenced by the site of integration even when they carry their own promoter elements and transcription factor binding sites. The cytomegalovirus (CMV) promoter, a strong promoter often used for transgene expression in mammalian cells in cul...

Full description

Saved in:
Bibliographic Details
Published in:Gene 2009, Vol.428 (1), p.20-24
Main Authors: Mehta, Abhishek Kumar, Majumdar, Subeer S., Alam, Parwez, Gulati, Neerja, Brahmachari, Vani
Format: Article
Language:English
Subjects:
Animals
Antigens, Viral - genetics
Antigens, Viral - metabolism
Cells, Cultured
Chromatin - metabolism
Chromatin Immunoprecipitation
CpG Islands
Cytomegalovirus
Cytomegalovirus - genetics
DNA Methylation
Epigenesis, Genetic
Gene Expression Regulation, Viral
Gene Silencing
Green Fluorescent Proteins - metabolism
Histone Deacetylases
Histone methylation
Histones - metabolism
Humans
Immediate-Early Proteins - genetics
Immediate-Early Proteins - metabolism
Integration site
Kidney - cytology
Kidney - metabolism
MeCP2
Methyl-CpG-Binding Protein 2 - genetics
Methyl-CpG-Binding Protein 2 - metabolism
Mice
Mice, Transgenic
Position effect
Promoter Regions, Genetic - genetics
Regulatory Sequences, Nucleic Acid
Transgene silencing
Virus Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The expression of genes in transgenic mice is known to be influenced by the site of integration even when they carry their own promoter elements and transcription factor binding sites. The cytomegalovirus (CMV) promoter, a strong promoter often used for transgene expression in mammalian cells in culture, is known to be silenced by DNA methylation and histone deacetylation but there is no report on the role of histone methylations in its regulation. We generated two transgenic lines carrying green florescence protein coding gene as reporter driven by cytomegalovirus major immediate-early promoter/enhancer. We observe that silencing of CMV promoter is dependent on the site of transgene integration, except in testis, and the nature of DNA and histone methylations strongly correlate with the expression status of the reporter. We find that silenced CMV promoter interacts in vivo, with Methyl CpG binding protein 2 (MeCP2), a recruiter of histone deacetylases (HDACs) and histone (H3K9) methyl transferase. Histone H3K4methylation, the active chromatin mark, is also associated with silenced promoter, suggesting bivalent marking of the promoter and its susceptibility to reactivation on induction.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2008.09.033