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

• Published in: EMBO reports Vol. 22; no. 8; pp. e52462 - n/a
• Main Authors: Jiang, Xuanzhao, Wen, Jiayu, Paver, Elizabeth, Wu, Yu-Huan, Sun, Gege, Bullman, Amanda, Dahlstrom, Jane E, Tremethick, David J, Soboleva, Tatiana A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.08.2021; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Accessibility; Alternative splicing; Biosynthesis; Cancer; Cell growth; Cell proliferation; Chromatin; Chromatin - genetics; Deoxyribonucleic acid; Depletion; DNA; DNA-directed RNA polymerase; Ectopic expression; EMBO03; EMBO09; Enrichment; Gene expression; Genes; H2A.B; histone variants; Histones; Histones - genetics; Hodgkin Disease - genetics; Hodgkin's lymphoma; Humans; Lymphoma; Male; Nucleoli; Proteins; Ribonucleic acid; Ribosomal DNA; Ribosomal proteins; Ribosomes - genetics; RNA; RNA polymerase I and II; Splicing; Testis; Transcription; Tumor cell lines; Yeast; RNA polymerase I and II; histone variants; transcription; chromatin; H2A.B
• ISSN: 1469-221X; 1469-3178; 1469-3178
• DOI: 10.15252/embr.202152462

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. SYNOPSIS The eutherian testis-specific histone variant H2A.B is aberrantly expressed in Hodgkin Lymphoma and enhances ribosomal biogenesis by stimulating both RNA Pol I transcription and the transcription of ribosomal protein genes. H2A.B is required for the high cell proliferation rate of Hodgkin Lymphoma cell lines. H2A.B is enriched in rDNA chromatin and interacts with RNA Pol I. H2A.B is required for transcription and alternative splicing of genes that are linked to cancer such as ribosomal proteins. The chromatin accessibility of active genes is enhanced by H2A.B. Graphical Abstract The eutherian testis-specific histone variant H2A.B is aberrantly expressed in Hodgkin Lymphoma and enhances ribosomal biogenesis by stimulating both RNA Pol I transcription and the transcription of ribosomal protein genes.