Epstein-Barr nuclear antigen leader protein coactivates transcription through interaction with histone deacetylase 4.
Epstein-Barr nuclear antigen leader protein coactivates transcription through interaction with histone deacetylase 4.
复制标题
Epstein-Barr 核抗原前导蛋白通过与组蛋白脱乙酰酶 4 相互作用来共激活转录。
DOI：
10.1073/pnas.0609320103
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发表时间：
2006
影响因子：
11.1
通讯作者：
Kieff,E
中科院分区：
文献类型：
--
作者：
Portal,D;Rosendorff,A;Kieff,E
Epstein-Barr核抗原（EBNA）先导蛋白（ebnap）与EBNA2协同激活启动子，对eb病毒在B细胞的永生化起重要作用。对组蛋白去乙酰化酶（HDACs）在EBNALP和EBNA2启动子调控中的作用的研究已经在淋巴母细胞样细胞系中发现EBNALP和EBNA2与HDAC4相关。此外，转录缺陷EBNALP点突变体与HDAC4没有关联。HDAC4和hdac5过表达抑制EBNA2激活和EBNALP共激活，而其他HDACs的作用不大。EBNALP表达降低细胞核HDAC4。14-3-3的表达将HDAC4锚定在细胞质中，增强EBNALP的作用，逆转HDAC4或5的抑制。HDAC4逆转依赖于HDAC4核输出序列。与核HDAC4缺失介导的EBNALP共激活一致，HDAC4过表达增加核HDAC4并特异性抑制ebna2依赖性激活以及EBNALP依赖性共激活。此外，EBNALP、HDAC4和14-3-3可以在一个复合物中免疫沉淀。因此，这些数据有力地支持了ebnap通过将HDAC4和5从EBNA2激活的启动子重新定位到细胞质中来共同激活转录的模型。观察到的EBNALP效应也可能部分通过HDAC5，它与HDAC4高度同源。
Epstein–Barr nuclear antigen (EBNA) leader protein (EBNALP) coactivates promoters with EBNA2 and is important for Epstein–Barr virus immortalization of B cells. Investigation of the role of histone deacetylases (HDACs) in EBNALP and EBNA2 promoter regulation has now identified EBNALP and EBNA2 to be associated with HDAC4 in a lymphoblastoid cell line. Furthermore, a transcription-deficient EBNALP point mutant did not associate with HDAC4. HDAC4 and 5 overexpression repressed EBNA2 activation and EBNALP coactivation, whereas other HDACs had little effect. Moreover, EBNALP expression decreased nuclear HDAC4. Expression of 14-3-3 anchors HDAC4 in the cytoplasm, increased EBNALP effects, and reversed HDAC4 or 5 repression. HDAC4 reversal depended on the HDAC4 nuclear export sequence. Consistent with EBNALP coactivation being mediated by nuclear HDAC4 depletion, HDAC4 overexpression increased nuclear HDAC4 and specifically repressed EBNA2-dependent activation as well as EBNALP-dependent coactivation. Also, EBNALP, HDAC4, and 14-3-3 could be immunoprecipitated in a single complex. Thus, these data strongly support a model in which EBNALP coactivates transcription by relocalizing HDAC4 and 5 from EBNA2 activated promoters to the cytoplasm. The observed EBNALP effects are likely also in part through HDAC5, which is highly homologous to HDAC4.