Nat Commun:短H2A组蛋白突变体在癌症中表达并表现癌蛋白特性

2021-01-28 xiaozeng MedSci原创

核小体是染色质的基本亚基,由组蛋白八聚体(H2A、H2B、H3和H4)组成。在许多不同的恶性肿瘤中发现了组蛋白中的单等位基因突变,突变蛋白也被称为“癌蛋白”。

核小体是染色质的基本亚基,由组蛋白八聚体(H2A、H2B、H3和H4)组成。在许多不同的恶性肿瘤中发现了组蛋白中的单等位基因突变,突变蛋白也被称为“癌蛋白”。癌蛋白在总组蛋白库中的占比很小,很少能够通过自身引起癌症的发生。相反的,其能够与其他癌基因协同作用,促进肿瘤染色质景观的发展。

近期的大规模癌症基因组分析确定了许多常见癌症中高度保守的组蛋白折叠域(HFD)内的复发突变。这些HFD突变,包括特征明确的H2B-E76K突变,会降低核小体的稳定性,并干扰染色质。


sH2A(短的组蛋白H2A突变体)是一类在哺乳动物精子发生过程中表达的组蛋白突变体。目前尚不清楚其在正常睾丸的表达调控。 在该研究中,研究人员发现sH2A与核小体的不稳定和交替剪接机制的调节相关。

H2A.B在多种癌症中都有表达

研究人员通过对种系的短H2A序列和野生型H2A中癌蛋白相关突变的比较分析,研究人员发现sH2A蛋白具有类似于与核小体不稳定性相关的复发性癌基因突变的特征,即具有固有的癌蛋白特征,其中最典型的sH2A突变蛋白为H2A.B。


通过对几种现有的癌症基因组学数据集的分析,研究人员发现在各种癌症中sH2A的异常上调。进一步的研究显示,该表达上调与这些癌症中核小体稳定性失衡的独特的相关剪接特征相关。

具有H2A.B活性癌症中的剪接分析

综上,该研究结果显示,短的H2A蛋白是一类“现成的”癌蛋白,其异常表达会导致癌症中的染色质功能障碍。


原始出处:

Chew, GL., Bleakley, M., Bradley, R.K. et al. Short H2A histone variants are expressed in cancer. Nat Commun 12, 490 (20 January 2021).

 

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    2021-10-25 liye789132251
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    2021-07-09 liuli5079
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    2021-01-30 xqptu
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    2021-01-28 wxl882001

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