The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains.
The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes through separate domains.
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潜伏期相关核抗原通过不同的结构域与 MeCP2 和核小体相互作用。
DOI：
10.1128/jvi.01097-09
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发表时间：
2010
影响因子：
5.4
通讯作者：
Wilson,AngusC
中科院分区：
文献类型：
--
作者：
Matsumura,Satoko;Persson,LindaM;Wong,LaiYee;Wilson,AngusC
卡波西肉瘤相关疱疹病毒 (KSHV) 感染的细胞表达潜伏相关核抗原 (LANA)，参与宿主和病毒基因表达的调节以及 KSHV 潜伏附加体的维持。这些不同功能的执行涉及位于 LANA 氨基末端的 7 个氨基酸染色质结合基序 (CBM)，该基序能够直接与核小体结合。 LANA 与其他染色质成分相互作用，包括甲基 CpG 结合蛋白 2 (MeCP2)。在这里，我们表明 LANA 的羧基末端 DNA 结合/二聚化结构域提供了与 MeCP2 的主要相互作用，但这种关联受到 CBM 的调节。 LANA 需要这两个结构域与 MeCP2 在染色质中心共定位，染色质中心是广泛的中心周异染色质区域，可以通过荧光显微镜成像。在 MeCP2 中，甲基 CpG 结合域 (MBD) 是染色质定位的主要决定因素，并与相邻的抑制域（转录抑制域 [TRD] 和辅阻遏物相互作用域 [CRID]）一起作用，将 LANA 重定向到染色中心。 MeCP2 有助于通过与 KSHV 末端重复序列结合的 LANA 进行抑制，除了 MBD 和 CRID/TRD 之外，该功能还需要 MeCP2 C 末端。 LANA和MeCP2还可以协同刺激人类E2F1启动子的转录，该启动子缺乏LANA DNA结合序列，但该功能需要LANA的N端和C端。 LANA 与组蛋白和染色质结合蛋白（如 MeCP2）建立多价相互作用的能力将使 LANA 能够将调节复合物引导至特定的染色体位点，从而实现潜伏感染细胞中细胞基因表达的稳定重编程。
Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells express the latency-associated nuclear antigen (LANA) involved in the regulation of host and viral gene expression and maintenance of the KSHV latent episome. Performance of these diverse functions involves a 7-amino-acid chromatin-binding motif (CBM) situated at the amino terminus of LANA that is capable of binding directly to nucleosomes. LANA interacts with additional chromatin components, including methyl-CpG-binding protein 2 (MeCP2). Here, we show that the carboxy-terminal DNA-binding/dimerization domain of LANA provides the principal interaction with MeCP2 but that this association is modulated by the CBM. Both domains are required for LANA to colocalize with MeCP2 at chromocenters, regions of extensive pericentric heterochromatin that can be imaged by fluorescence microscopy. Within MeCP2, the methyl-CpG-binding domain (MBD) is the primary determinant for chromatin localization and acts together with the adjacent repression domains (the transcription repression domain [TRD] and the corepressor-interacting domain [CRID]) to redirect LANA to chromocenters. MeCP2 facilitates repression by LANA bound to the KSHV terminal repeats, a function that requires the MeCP2 C terminus in addition to the MBD and CRID/TRD. LANA and MeCP2 can also cooperate to stimulate transcription of the human E2F1 promoter, which lacks a LANA DNA-binding sequence, but this function requires both the N and C termini of LANA. The ability of LANA to establish multivalent interactions with histones and chromatin-binding proteins such as MeCP2 would enable LANA to direct regulatory complexes to specific chromosomal sites and thereby achieve stable reprogramming of cellular gene expression in latently infected cells.