Regulation of the Epstein-Barr virus Zp promoter in B lymphocytes during reactivation from latency.
Ten novel mutations were introduced into the Zp promoter to test the role of sequences outside the established transcription factor-binding sites in Epstein-Barr virus (EBV) reactivation. Most of these had only small effects, but mutations in the ZID site were shown to reduce Zp activity strongly at early times after induction by anti-immunoglobulin (anti-Ig). The binding of MEF2 transcription factor to ZID was characterized in detail and linked functionally to Zp promoter activity. The presence of XBP-1s, the active form of XBP-1, after administration of anti-Ig to Akata Burkitt's lymphoma cells is consistent with a role for this factor in reactivation of the EBV lytic cycle, although signalling through MEF2D was quantitatively much more significant in activation of Zp. Silencing of Zp during latency is thought to be primarily a consequence of a repressive chromatin structure on Zp, and this aspect of Zp regulation can be observed in the Akata genome through protection of Zp from activation by BZLF1 in the absence of signalling from the B-cell receptor.
McDonald
Carol
C
Department of Virology, Imperial College Faculty of Medicine, St Mary's Campus, London W2 1PG, UK.
Karstegl
Claudio Elgueta
CE
Kellam
Paul
P
Farrell
Paul J
PJ
D001402:B-Lymphocytes / Q000821:virology*; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D026161:MADS Domain Proteins / Q000378:metabolism; D064326:MEF2 Transcription Factors; D009154:Mutation; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014775:Virus Activation; D000071717:X-Box Binding Protein 1
C063676:BZLF1 protein, Herpesvirus 4, Human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human