Latency-associated nuclear antigen 1 (LANA-1) of Kaposi's sarcoma-associated herpesvirus (KSHV) mediates the episomal replication of the KSHV genome, as well as transcriptional regulation, in latently infected cells. Interaction of LANA-1 with cellular chromatin is required for both these functions. An N-terminal heterochromatin-binding site in LANA-1 is essential for the replication and maintenance of latent episomes, as well as transcriptional regulation. We have recently described a C-terminal domain in LANA-1 that modulates the interaction with cellular interphase chromatin or elements of the nuclear matrix. Here, we used a series of LANA-1 deletion mutants to investigate the relationship between the different functions of LANA-1 and its interaction with the host chromatin-binding protein Brd2/RING3. Our findings suggest that the C-terminal chromatin-binding domain in LANA-1 is required for multiple LANA-1 functions, including the ability to bind to and replicate viral episomal DNA, to modulate transcription, and to interact with Brd2/RING3. Similar to the recently described tethering of bovine papillomavirus E2 protein to host chromatin via Brd4/MCAP, Brd2/RING3, another member of the Brd family of chromatin-binding proteins, therefore interacts with a chromatin-binding region of another viral latent nuclear protein and could play a role in its multiple functions.

中文翻译：

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Brd2 / RING3与卡波济氏肉瘤相关疱疹病毒潜伏期相关核抗原1（LANA-1）中的染色质结合域相互作用，这是LANA-1多种功能所必需的。

卡波西氏肉瘤相关疱疹病毒（KSHV）的潜伏期相关核抗原1（LANA-1）介导了潜伏感染细胞中KSHV基因组的游离复制和转录调控。这两种功能都需要LANA-1与细胞染色质的相互作用。LANA-1中的N端异染色质结合位点对于潜在的附加体的复制和维持以及转录调控至关重要。我们最近在LANA-1中描述了一个C末端域，该域调节与细胞间相染色质或核基质元素的相互作用。在这里，我们使用了一系列的LANA-1缺失突变体来研究LANA-1的不同功能与其与宿主染色质结合蛋白Brd2 / RING3的相互作用之间的关系。我们的发现表明，LANA-1的C端染色质结合域是多种LANA-1功能所必需的，这些功能包括与病毒游离DNA结合和复制，调节转录以及与Brd2 / RING3相互作用的能力。类似于最近描述的牛乳头瘤病毒E2蛋白通过Brd4 / MCAP，Brd2 / RING3，即染色质结合蛋白的Brd家族的另一个成员，通过系留于染色质的系链，与另一个病毒潜伏核蛋白的染色质结合区相互作用，并且可以在其多种功能中发挥作用。