报告题目：The Genomic Landscape of Epstein–Barr virus nuclear antigens in Lymphoblastoid B Cells
报告时间：2016/10/20，星期四，下午3:30-5:00
报告地点：生物楼一楼中厅
报 告 人：Hufeng Zhou，Harvard Medical School
内容简介：
Epstein–Barr virus (EBV) nuclear antigens including EBNALP (LP), EBNA3A(E3A), EBNA3C(E3C)
and EBNA2 (E2) are coexpressed in EBV-infected B lymphocytes and are critical for lymphoblastoid
cell line outgrowth. LP removes NCOR and RBPJ repressive complexes from promoters, enhancers,
and matrix-associated deacetylase bodies, whereas E2 activates transcription from distal enhancers.
Our studies show that LP/E2 sites were more similar to LP than to E2 sites in associated cell TFs,
RNAPII, P300, and histone H3K4me3, H3K9ac, H3K27ac, and H2Az occupancy, and were more
highly transcribed than LP or E2 sites. Gene affected by CTCF and LP cooccupancy were more highly
expressed than genes affected by CTCF alone. LP was at myc enhancers and promotersand MYC
regulated cell survival genes. EBNA3A sites clustered into seven unique groups, with differing B-cell
TFs and epigenetic marks. EBNA3A coincidence with BATF-IRF4 or RUNX3 was associated with
stronger EBNA3A ChIP-Seq signals. EBNA3A was at MYC,CDKN2A/B, CCND2, CXCL9/10, and
BCL2, together with RUNX3, BATF, IRF4, and SPI1. EBNA3C signals were strongest at BATF/IRF4
and SPI1/IRF4 composite sites. EBNA3C bound strongly to the p14 ARF promoter through
SPI1/IRF4/BATF/RUNX3, establishing RBPJ-, Sin3A-, and REST-mediated repression. These data
implicate LP and associated TFs and DNA looping factors CTCF, RAD21, and YY1chromatin
remodeling complexes in repressor depletion and gene activation necessary for lymphoblastoid cell line
growth and strongly support a model in which EBNA3A and EBNA3C are tethered to DNA through a
BATF-containing protein complexes to enable continuous cell proliferation.
