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bioRxiv · 10.1101/2020.10.22.350108

Epstein-Barr virus promotes survival through germinal center light zone chromatin architecture

Dai, J.·Heckenberg, E.·Song, L.·Crawford, G.·Luftig, M. A.
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Abstract

BFL-1 is an understudied anti-apoptotic protein upregulated in cancer and Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs). We have previously shown that BFL-1 is regulated through viral EBNA3A-mediated alterations in B-cell chromatin conformation (Price et al., 2017). Here, we extend those findings to define cis- and trans-acting factors that regulate BFL-1 in LCLs and reliance on BFL-1 for survival from extrinsic apoptosis. Beyond LCLs, BFL-1 is expressed in B cells maturing in the germinal center (GC). We therefore characterized the gene expression profiles and chromatin landscape of maturing human tonsillar B-cell subsets. While chromatin accessibility at the BFL-1 locus increases as naive B cells enter the GC reaction, BFL-1 expression increases during the transition from dark zone to light zone (LZ) correlating with association between enhancer regions and the transcriptional start site. The relationship between LCLs and LZ B cells suggests that EBV phenocopies GC biology to enhance their survival in establishing latent infection.

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Dai, J., Heckenberg, E., Song, L., Crawford, G., Luftig, M. A.. 2020-10-22. Epstein-Barr virus promotes survival through germinal center light zone chromatin architecture. https://doi.org/10.1101/2020.10.22.350108

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