EBV-Associated Lymphoma Consortium Annual Meeting (Abstract)

Abstract Submission

Submission information

Submission Number: 4

Submission ID: 150768

Submission UUID: 3c6f0dbc-efc3-4dbb-9ea0-27aaa8c50684

Submission URI: /nci/ealv/venue/abstract

Submission Update: /nci/ealv/venue/abstract?token=64aPD2WhlZzZdzmakmTE2bhiqBlRnyHX_DQ85sXpams

Created: Wed, 09/03/2025 - 13:22

Completed: Wed, 09/03/2025 - 13:22

Changed: Wed, 09/03/2025 - 13:22

Remote IP address: 10.208.28.30

Submitted by: Anonymous

Language: English

Is draft: No

Webform: EBV-Associated Lymphoma Consortium Annual Meeting (Abstracts)

Submitted to: EBV-Associated Lymphoma Consortium Annual Meeting (Abstract)

OMB No.: 0925-0740
Expiration Date: 9/30/2025

Public reporting burden for this collection of information is estimated to average 60 minutes per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to: NIH, Project Clearance Branch, 6705 Rockledge Drive, MSC 7974, Bethesda, MD 20892-7974, ATTN: PRA (0925-0740). Do not return the completed form to this address.

Presenter Information

Please enter information for the person who will be the primary presenter/speaker/author.

First Name

Middle Initial

Last Name

Degree(s)

Please use the following formatting for these degrees: M.D. Ph.D. MPH

Position/Title/Career Status

Organization

Organization City/Town

Please provide a contact email for conference organizers to reach you.

Abstract Information

Abstract Keywords

Up to five keywords of your choice

Abstract Title

Abstract 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.