Transcriptional regulation of Bcl-2 gene by the PR/SET domain family member PRDM10
Transcriptional regulation of Bcl-2 gene by the PR/SET domain family member PRDM10
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DOI：
10.7717/peerj.6941
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发表时间：
2019-05-15
期刊：
影响因子：
2.7
通讯作者：
Huang, Shi
中科院分区：
文献类型：
--
作者：
Chen, Na;Hu, Taobo;Huang, Shi
Bcl2(B细胞淋巴瘤2)蛋白定位于线粒体外膜，在促进细胞存活和抑制促凋亡蛋白的作用中发挥重要作用。PRDM10是表观遗传调节因子PR/SET家族中的一员，可能在发育和细胞分化中发挥作用。在此，我们证明了人PRDM10参与了人Bcl2基因的转录调控。我们发现PRDM10在人细胞中的缺失降低了Bcl2蛋白的表达，而PRDM10的过表达促进了Bcl2蛋白的表达。此外，在PRDM10共转染细胞中，Bcl2基因P1启动子的荧光素酶报告活性显著增强，并且PRDM10在体内能够与Bcl2P1启动子结合。使用癌症基因组图谱(TCGA)数据集，我们发现在包括乳腺癌、结肠癌和肺癌组织在内的几种癌症类型中，PRDM10和Bcl-2之间存在微弱的正相关性。这些数据确定了PRDM10蛋白的一个新功能，并为转录调控Bcl2的表达提供了新的见解。
Bcl-2 (B-cell lymphoma 2) protein is localized in the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins. PRDM10 is a member of the PR/SET family of epigenetic regulators and may play a role in development and cell differentiation. Here we show that human PRDM10 contributes to the transcriptional regulation of human Bcl-2 gene. We found that PRDM10-depletion in human cells reduced the expression of Bcl-2 protein and over-expression of PRDM10 promoted Bcl-2 protein expression. Furthermore, luciferase reporter activity of Bcl-2 gene P1 promoter was significantly increased in cells co-transfected with PRDM10, and PRDM10 was able to bind to the Bcl-2 P1 promoter in vivo. Using The Cancer Genome Atlas (TCGA) data set, we found weak positive correlation between PRDM10 and Bcl-2 in several cancer types including cancers of the breast, colon, and lung tissues. These data identify a novel function for PRDM10 protein and provide insights on the transcriptional control of Bcl-2 expression.