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. Using two HL-derived cell lines derived from different subtypes of HL, H2A.B knockdown inhibited cell proliferation. H2A.B was enriched in both the nucleoli of these HL cell lines and primary HL samples. 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.

中文翻译：

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H2A.B是参与霍奇金淋巴瘤核糖体生物发生活化的癌症/睾丸因子

睾丸特异的染色质功能调节剂通常在人类癌症中异位表达，但对其作用了解甚少。对81例原发性霍奇金淋巴瘤（HL）样本进行的检查显示，欧氏睾丸特异性组蛋白变体H2A.B的异位表达是HL的固有特征。使用两种衍生自HL不同亚型的HL衍生细胞系，H2A.B抑制可抑制细胞增殖。H2A.B富含这些HL细胞系和原发性HL样品的核仁。H2A.B增强了核糖体DNA（rDNA）的转录，在rDNA启动子和转录区域富集，并与RNA Pol I相互作用。H2A.B的耗尽导致rDNA染色质丢失RNA PolI。值得注意的是，H2A。位于转录起始位点和基因体内的高水平核糖体蛋白基因表达也需要B。H2A.B组合式降低活性RNA Pol II基因的基因体染色质可及性，同时减少转录。两者合计，我们的数据表明，在HL H2A.B中获得了新功能，即增加核糖体生物发生的能力。