高迁移率族蛋白 B4 由神经元细胞表达，并影响涉及神经分化的基因的表达。
HMGB4 is expressed by neuronal cells and affects the expression of genes involved in neural differentiation.
机构信息
Neuroscience center, University of Helsinki, Finland.
Department of Biosciences, University of Helsinki, Finland.
出版信息
Sci Rep. 2016 Sep 9;6:32960. doi: 10.1038/srep32960.
HMGB4 is a new member in the family of HMGB proteins that has been characterized in sperm cells, but little is known about its functions in somatic cells. Here we show that HMGB4 and the highly similar rat Transition Protein 4 (HMGB4L1) are expressed in neuronal cells. Both proteins had slow mobility in nucleus of living NIH-3T3 cells. They interacted with histones and their differential expression in transformed cells of the nervous system altered the post-translational modification statuses of histones in vitro. Overexpression of HMGB4 in HEK 293T cells made cells more susceptible to cell death induced by topoisomerase inhibitors in an oncology drug screening array and altered variant composition of histone H3. HMGB4 regulated over 800 genes in HEK 293T cells with a p-value ≤0.013 (n = 3) in a microarray analysis and displayed strongest association with adhesion and histone H2A -processes. In neuronal and transformed cells HMGB4 regulated the expression of an oligodendrocyte marker gene PPP1R14a and other neuronal differentiation marker genes. In conclusion, our data suggests that HMGB4 is a factor that regulates chromatin and expression of neuronal differentiation markers.
HMGB4 是 HMGB 蛋白家族中的一个新成员，它在精子细胞中已被鉴定，但在体细胞中其功能知之甚少。在这里，我们表明 HMGB4 和高度相似的大鼠转换蛋白 4（HMGB4L1）在神经元细胞中表达。这两种蛋白质在活 NIH-3T3 细胞的核中具有较慢的迁移率。它们与组蛋白相互作用，其在神经系统转化细胞中的差异表达改变了组蛋白在体外的翻译后修饰状态。在 HEK 293T 细胞中过表达 HMGB4 会使细胞在肿瘤药物筛选阵列中更容易受到拓扑异构酶抑制剂诱导的细胞死亡，并改变组蛋白 H3 的变体组成。HMGB4 在 HEK 293T 细胞中调节了超过 800 个基因，在微阵列分析中 p 值≤0.013（n=3），与粘附和组蛋白 H2A 过程具有最强的关联。在神经元和转化细胞中，HMGB4 调节少突胶质细胞标记基因 PPP1R14a 和其他神经元分化标记基因的表达。总之，我们的数据表明 HMGB4 是一种调节染色质和神经元分化标记物表达的因子。
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