KSHV RTA induces a transcriptional repressor, HEY1 that represses rta promoter.
KSHV RTA induces a transcriptional repressor, HEY1 that represses rta promoter.
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DOI：
10.1016/j.bbrc.2006.04.092
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发表时间：
2006-06
影响因子：
3.1
通讯作者：
Kaori Yada;E. Do;S. Sakakibara;Eriko Ohsaki;E. Ito;Shinya Watanabe;K. Ueda
中科院分区：
文献类型：
--
作者：
Kaori Yada;E. Do;S. Sakakibara;Eriko Ohsaki;E. Ito;Shinya Watanabe;K. Ueda
卡波西肉瘤相关疱疹病毒 (KSHV) 是一种 γ-疱疹病毒，通常与卡波西肉瘤和原发性渗出性淋巴瘤等肿瘤的形成有关。 KSHV RTA 是 KSHV 感染细胞中裂解复制/重新激活所必需的。我们开发了诱导型 RTA 表达细胞系来寻找 RTA 诱导基因。使用DNA芯片技术，我们发现hey1（一种含有基本螺旋-环-螺旋的转录因子）在该品系中增加了三到四倍。在荧光素酶报告系统中，RTA 激活了多种细胞系中的 hey1 启动子；相反，HEY1 抑制 rta 启动子。染色质免疫沉淀测定表明，HEY 不直接结合 rta 启动子，尽管它可能作为复合物的一部分抑制 rta 表达。因此，hey1 可能有助于在裂解复制/重新激活过程中表达爆发后下调 RTA。类似的抑制机制可能会下调其他疱疹病毒的早期基因表达，尽管可能涉及不同的转录因子。
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a γ-herpesvirus that is frequently associated with the formation of tumors like Kaposi’s sarcoma and primary effusion lymphomas. KSHV RTA is required for lytic replication/reactivation in KSHV-infected cells. We developed an inducible RTA expression cell line to search for RTA-inducible genes. Using DNA chip technology, we showed that hey1, a basic helix-loop-helix-containing transcription factor, increased three- to fourfold in this line. In a luciferase reporter system, RTA activated the hey1 promoter in several cell lines; conversely, HEY1 repressed the rta promoter. Chromatin immunoprecipitation assays indicated that HEY did not bind the rta promoter directly, although it may repress rta expression as part of a complex. Thus, hey1 may help to downregulate RTA after its burst of expression during lytic replication/reactivation. Similar repression mechanisms may downregulate immediate-early gene expression in other herpesviruses, although different transcription factors are probably involved.