EBV-Associated Lymphoma Consortium Annual Meeting (Abstract): Submission #4

serial: '4'
sid: '150768'
uuid: 3c6f0dbc-efc3-4dbb-9ea0-27aaa8c50684
uri: /nci/ealv/venue/abstract
created: '1756920154'
completed: '1756920154'
changed: '1756920154'
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data:
  degree_s_: 'MD, PhD'
  email: bgewurz@bwh.harvard.edu
  first_name: Ben
  keywords_abstracts: ''
  last_name: Gewurz
  middle_initial: E.
  organization: "Brigham & Women's Hospital"
  organization_address:
    address: ''
    address_2: ''
    city: Boston
    country: ''
    postal_code: ''
    state_province: ''
  summary: 'Much remains to be learned about how EBV latency genes and host epigenetic factors cross-regulate one-another, with relevance to the development of novel host-targeted therapeutic approaches. While linker histone H1 are B-cell tumor suppressors mutated with striking frequency across EBV-negative lymphomas, little is known about histone H1 roles in EBV-mediated lymphomagenesis and lymphomas, how EBV latency genes suppress H1 expression or how H1 in turn cross-regulates the EBV epigenome. We build upon our observation that EBV strongly reduces linker histone H1 expression in newly infected B-cells as they transform into lymphoblastoid cells with the latency III program and in lymphoblastoid cell lines. We characterized how EBV suppresses histone H1 expression in B cell transformation. ATACseq highlighted that EBV latency III reduced H1 gene chromatin accessibility in Burkitt B cells, but not in newly transformed peripheral blood B cells or in LCLs. Histone H1 genes retained activating chromatin marks following B cell EBV infection and in LCLs. Instead, we observed reduction in histone H1 locus long-range chromatin contacts. While infection by EBNA3A/C double knockout (KO) EBV reduced H1 gene chromatin accessibility in LCLs, we observed increased H1 gene expression in B cells infected by EBNA3A KO EBV. However, EBV must maintain a some H1 expression to maintain viral latency. Relatedly, we investigated how H1 abundance correlated with B cell genome-wide H3K36me2 and H3K27me3 epigenetic marks, since the H3K36me2 epigenetic writers compete with H1 at DNA sites, whereas H1 promotes repressive H3K27me3 deposition to silence target genes. We used ChIP-seq to define target genes with the most differential H3K36me2 and H3K27me3 marks in latency I vs III states with elevated versus repressed H1 expression, respectively. Together, these studies provide key insights into how EBV latency genes and linker histone H1 cross-regulate one-another.'
  title: 'Associate Professor'
  ttile: 'EBV Latency Gene and Linker Histone H1 Cross-regulation in B cell lymphomagenesis'