MEF2-mediated recruitment of class II HDAC at the EBV immediate early gene BZLF1 links latency and chromatin remodeling.
In B lymphocytes induced to proliferate in vitro by the Epstein-Barr virus (EBV), extra-chromosomal viral episomes packaged in chromatin persist in the nucleus, and there is no productive cycle. A switch from this latency to the productive cycle is observed after induced expression of the EBV BZLF1 gene product, the transcription factor EB1. We present evidence that, during latency, proteins of the myocyte enhancer binding factor 2 (MEF2) family are bound to the BZLF1 promoter and recruit class II histone deacetylases. Furthermore, we propose that latency is determined primarily by a specific and local recruitment of class II histone deacetylase (HDAC) by MEF2D to the BZLF1 gene promoter. The switch from latency to the productive cycle could be due in part to post-translational modification of MEF2 proteins and changes in the local acetylation state of the chromatin.
Gruffat
H
H
Laboratoire de virologie humaine, INSERM U412, ENS-Lyon, 46 allée d'Italie, F-69364 Lyon, France. hgruffat@ens-lyon.fr
Manet
E
E
Sergeant
A
A
D001402:B-Lymphocytes / Q000502:physiology; D002460:Cell Line; D002843:Chromatin / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006655:Histone Deacetylases / Q000502:physiology*; D006657:Histones / Q000502:physiology; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014764:Viral Proteins; D017735:Virus Latency / Q000502:physiology*; D014779:Virus Replication
C063676:BZLF1 protein, Herpesvirus 4, Human; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578043:MEF2D protein, human; D018006:Myogenic Regulatory Factors; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D006655:Histone Deacetylases