Identification and analysis of papillomavirus E2 protein binding sites in the human genome.
Papillomavirus E2 protein is required for the replication and maintenance of viral genomes and transcriptional regulation of viral genes. E2 functions through sequence-specific binding to 12-bp DNA motifs-E2 binding sites (E2BS)-in the virus genome. Papillomaviruses are able to establish persistent infection in their host and have developed a long-term relationship with the host cell in order to guarantee the propagation of the virus. In this study, we have analyzed the occurrence and functionality of E2BSs in the human genome. Our computational analysis indicates that most E2BSs in the human genome are found in repetitive DNA regions and have G/C-rich spacer sequences. Using a chromatin immunoprecipitation approach, we show that human papillomavirus type 11 (HPV11) E2 interacts with a subset of cellular E2BSs located in active chromatin regions. Two E2 activities, sequence-specific DNA binding and interaction with cellular Brd4 protein, are important for E2 binding to consensus sites. E2 binding to cellular E2BSs has a moderate or no effect on cellular transcription. We suggest that the preference of HPV E2 proteins for E2BSs with A/T-rich spacers, which are present in the viral genomes and underrepresented in the human genome, ensures E2 binding to specific binding sites in the virus genome and may help to prevent extensive and possibly detrimental changes in cellular transcription in response to the viral protein.
Center of Biomedical Technology, Institute of Technology, University of Tartu, Tartu, Estonia.
Liisi
L
Võsa
Aleksander
A
Sudakov
Maido
M
Remm
Mart
M
Ustav
Reet
R
Kurg
D001665:Binding Sites; D018797:Cell Cycle Proteins; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human; D052140:Human papillomavirus 11 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D002843:Chromatin; D009687:Nuclear Proteins; D014157:Transcription Factors; D014764:Viral Proteins; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins; C117355:E2 protein, Human papillomavirus type 11