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

Date

2021

Authors

Jiang, Xuanzhao
Wen, Jiayu
Paver, Elizabeth
Wu, Yu-Huan
Sun, Gege
Bullman, A
Dahlstrom, Jane
Tremethick, David
Soboleva, Tatiana A

Journal Title

Journal ISSN

Volume Title

Publisher

Nature Publishing Group

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.

Description

Keywords

chromatin, H2A.B, histone variants, RNA polymerase I and II, transcription

Citation

Source

EMBO Reports

Type

Journal article

Book Title

Entity type

Access Statement

License Rights

DOI

10.15252/embr.202152462

Restricted until

2099-12-31