coordination of kshv latent and lytic gene control by ctcf-cohesin mediated chromosome conformation协调kshv潜伏和裂解基因控制ctcf-cohesin介导染色体构象.pdfVIP

Coordination of KSHV Latent and Lytic Gene Control by CTCF-Cohesin Mediated Chromosome Conformation 1,2 1 3 4 1 Hyojeung Kang , Andreas Wiedmer , Yan Yuan , Erle Robertson , Paul M. Lieberman * 1The Wistar Institute, Philadelphia, Pennsylvania, United States of America, 2 The Kyungpook National University, College of Pharmacy, Daegu, Korea, 3 The University of Pennsylvania, School of Dentistry, Philadelphia, Pennsylvania, United States of America, 4 The University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, United States of America Abstract Herpesvirus persistence requires a dynamic balance between latent and lytic cycle gene expression, but how this balance is maintained remains enigmatic. We have previously shown that the Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) major latency transcripts encoding LANA, vCyclin, vFLIP, v-miRNAs, and Kaposin are regulated, in part, by a chromatin organizing element that binds CTCF and cohesins. Using viral genome-wide chromatin conformation capture (3C) methods, we now show that KSHV latency control region is physically linked to the promoter regulatory region for ORF50, which encodes the KSHV immediate early protein RTA. Other linkages were also observed, including an interaction between the 59 and 39 end of the latency transcription cluster. Mutation of the CTCF-cohesin binding site reduced or eliminated the chromatin conformation linkages, and deregulated viral transcription and genome copy number control. siRNA depletion of CTCF or cohesin subunits also disrupted chromosomal linkages and deregulated viral latent and lytic gene transcription. Furthermore, the linkage between the latent and lytic control region was subject to cell cycl