The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression
The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression
复制标题
DOI：
10.1128/mcb.01435-07
复制
发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Rauscher, Frank J., III
中科院分区：
文献类型：
--
作者：
Hou, Zhaoyuan;Peng, Hongzhuang;Rauscher, Frank J., III
SNAIL转录因子含有C-末端串联锌指基序和N-末端SNAG抑制结构域。SNAIL家族的成员最近通过在胚胎发育和肿瘤进展期间调节上皮-间充质转化事件而成为发育和转移过程的主要贡献者。然而，SNAIL抑制基因表达的机制在很大程度上是不确定的。以前，我们证明了AJUBA家族的LIM蛋白作为辅助抑制SNAIL的功能，因此，可以作为一个平台的组装染色质修饰因子。在这里，我们描述了识别的蛋白质精氨酸甲基转移酶5（PRMT 5）作为一个效应招募到SNAIL通过与AJUBA的相互作用，其功能是抑制SNAIL靶基因，E-钙粘蛋白。PRMT 5与AJUBA的非LIM区域结合，并以SNAIL和AJUBA依赖性方式易位到细胞核中。p19细胞中PRMT 5的缺失刺激E-钙粘蛋白表达，并且可以在E-钙粘蛋白基因的近端启动子区域发现SNAIL、AJUBA和PRMT 5三元复合物，伴随着该基因座处组蛋白的精氨酸甲基化增加。总之，这些数据表明PRMT 5是SNAIL依赖性基因抑制的效应子。
The SNAIL transcription factor contains C-terminal tandem zinc finger motifs and an N-terminal SNAG repression domain. The members of the SNAIL family have recently emerged as major contributors to the processes of development and metastasis via the regulation of epithelial-mesenchymal transition events during embryonic development and tumor progression. However, the mechanisms by which SNAIL represses gene expression are largely undefined. Previously we demonstrated that the AJUBA family of LIM proteins function as corepressors for SNAIL and, as such, may serve as a platform for the assembly of chromatin-modifying factors. Here, we describe the identification of the protein arginine methyltransferase 5 (PRMT5) as an effector recruited to SNAIL through an interaction with AJUBA that functions to repress the SNAIL target gene, E-cadherin. PRMT5 binds to the non-LIM region of AJUBA and is translocated into the nucleus in a SNAIL-and AJUBA-dependent manner. The depletion of PRMT5 in p19 cells stimulates E-cadherin expression, and the SNAIL, AJUBA, and PRMT5 ternary complex can be found at the proximal promoter region of the E-cadherin gene, concomitant with increased arginine methylation of histones at the locus. Together, these data suggest that PRMT5 is an effector of SNAIL-dependent gene repression.