H2A.B is a cancer/testis factor involved in the activation of ribosome biogenesis in Hodgkin lymphoma

Xuanzhao Jiang, Jiayu Wen, Elizabeth Paver, Yu Huan Wu, Gege Sun, Amanda Bullman, Jane E Dahlstrom, David J. Tremethick*, Tatiana A. Soboleva*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    Abstract

    Testis-specific regulators of chromatin function are commonly ectopically expressed in human cancers, but their roles are poorly understood. Examination of 81 primary Hodgkin lymphoma (HL) samples showed that the ectopic expression of the eutherian testis-specific histone variant H2A.B is an inherent feature of HL. In experiments using two HL cell lines derived from different subtypes of HL, H2A.B knockdown inhibited cell proliferation. H2A.B was enriched in both nucleoli of these HL cell lines and primary HL samples. We found that H2A.B enhanced ribosomal DNA (rDNA) transcription, was enriched at the rDNA promoter and transcribed regions, and interacted with RNA Pol I. Depletion of H2A.B caused the loss of RNA Pol I from rDNA chromatin. Remarkably, H2A.B was also required for high levels of ribosomal protein gene expression being located at the transcriptional start site and within the gene body. H2A.B knockdown reduced gene body chromatin accessibility of active RNA Pol II genes concurrent with a decrease in transcription. Taken together, our data show that in HL H2A.B has acquired a new function, the ability to increase ribosome biogenesis.

    Original languageEnglish
    Article numbere52462
    JournalEMBO Reports
    Volume22
    Issue number8
    DOIs
    Publication statusPublished - 4 Aug 2021

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