cpg-methylation regulates a class of epstein-barr virus promoterscpg-methylation调节一类巴尔病毒启动子.pdfVIP

CpG-Methylation Regulates a Class of Epstein-Barr Virus Promoters 1 1 1 ¨ 1 2 Martin Bergbauer , Markus Kalla , Anne Schmeinck , Christine Gobel , Ulrich Rothbauer , Sebastian 3 ` 3 3 1 Eck , Anna Benets , Tim M. Strom , Wolfgang Hammerschmidt * ¨ 1 Department of Gene Vectors, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Munich, Germany, 2 Biocenter at the Department of ¨ Biology II, Ludwig-Maximilians University Munich, Martinsried, Germany, 3 Institute of Human Genetics, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany Abstract DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian gene regulation. In general, cytosine-phosphatidyl-guanosine (CpG)-methylated promoters are transcriptionally repressed and nuclear proteins such as MECP2, MBD1, MBD2, and MBD4 bind CpG-methylated DNA and contribute to epigenetic silencing. Methylation of viral DNA also regulates gene expression of Epstein-Barr virus (EBV), which is a model of herpes virus latency. In latently infected human B cells, the viral DNA is CpG-methylated, the majority of viral genes is repressed and virus synthesis is therefore abrogated. EBV’s BZLF1 encodes a transcription factor of the AP-1 family (Zta) and is the master gene to overcome viral gene repression. In a genome-wide screen, we now identify a