RT Journal Article
SR Electronic
T1 BZLF1 interacts with chromatin remodelers promoting escape from latent infections with EBV
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800108
DO 10.26508/lsa.201800108
VO 2
IS 2
A1 Marisa Schaeffner
A1 Paulina Mrozek-Gorska
A1 Alexander Buschle
A1 Anne Woellmer
A1 Takanobu Tagawa
A1 Filippo M. Cernilogar
A1 Gunnar Schotta
A1 Nils Krietenstein
A1 Corinna Lieleg
A1 Philipp Korber
A1 Wolfgang Hammerschmidt
YR 2019
UL https://www.life-science-alliance.org/content/2/2/e201800108.abstract
AB A hallmark of EBV infections is its latent phase, when all viral lytic genes are repressed. Repression results from a high nucleosome occupancy and epigenetic silencing by cellular factors such as the Polycomb repressive complex 2 (PRC2) and DNA methyltransferases that, respectively, introduce repressive histone marks and DNA methylation. The viral transcription factor BZLF1 acts as a molecular switch to induce transition from the latent to the lytic or productive phase of EBV’s life cycle. It is unknown how BZLF1 can bind to the epigenetically silenced viral DNA and whether it directly reactivates the viral genome through chromatin remodeling. We addressed these fundamental questions and found that BZLF1 binds to nucleosomal DNA motifs both in vivo and in vitro. BZLF1 co-precipitates with cellular chromatin remodeler ATPases, and the knock-down of one of them, INO80, impaired lytic reactivation and virus synthesis. In Assay for Transposase-Accessible Chromatin-seq experiments, non-accessible chromatin opens up locally when BZLF1 binds to its cognate sequence motifs in viral DNA. We conclude that BZLF1 reactivates the EBV genome by directly binding to silenced chromatin and recruiting cellular chromatin-remodeling enzymes, which implement a permissive state for lytic viral transcription. BZLF1 shares this mode of action with a limited number of cellular pioneer factors, which are instrumental in transcriptional activation, differentiation, and reprogramming in all eukaryotic cells.