The Epstein-Barr virus nuclear antigen-1 reprograms transcription by mimicry of high mobility group A proteins.
Viral proteins reprogram their host cells by hijacking regulatory components of protein networks. Here we describe a novel property of the Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA1) that may underlie the capacity of the virus to promote a global remodeling of chromatin architecture and cellular transcription. We found that the expression of EBNA1 in transfected human and mouse cells is associated with decreased prevalence of heterochromatin foci, enhanced accessibility of cellular DNA to micrococcal nuclease digestion and decreased average length of nucleosome repeats, suggesting de-protection of the nucleosome linker regions. This is a direct effect of EBNA1 because targeting the viral protein to heterochromatin promotes large-scale chromatin decondensation with slow kinetics and independent of the recruitment of adenosine triphosphate-dependent chromatin remodelers. The remodeling function is mediated by a bipartite Gly-Arg rich domain of EBNA1 that resembles the AT-hook of High Mobility Group A (HMGA) architectural transcription factors. Similar to HMGAs, EBNA1 is highly mobile in interphase nuclei and promotes the mobility of linker histone H1, which counteracts chromatin condensation and alters the transcription of numerous cellular genes. Thus, by regulating chromatin compaction, EBNA1 may reset cellular transcription during infection and prime the infected cells for malignant transformation.
Department of Cell and Molecular Biology, Karolinska Institutet, 17177 Stockholm, Sweden.
Giuseppe
G
Coppotelli
Nouman
N
Mughal
Simone
S
Callegari
Ramakrishna
R
Sompallae
Laia
L
Caja
Martijn S
MS
Luijsterburg
Nico P
NP
Dantuma
Aristidis
A
Moustakas
Maria G
MG
Masucci
D020816:Amino Acid Motifs; D000818:Animals; D034961:Antigens, Nuclear / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D053263:Gene Regulatory Networks; D024003:HMGA Proteins / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D059467:Transcriptome; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology
D034961:Antigens, Nuclear; D024003:HMGA Proteins; D006570:Heterochromatin; D006657:Histones; D019913:Nuclear Localization Signals; D014764:Viral Proteins