The Kruppel-like Zinc Finger Protein ZNF224 Recruits the Arginine Methyltransferase PRMT5 on the Transcriptional Repressor Complex of the Aldolase A Gene
The Kruppel-like Zinc Finger Protein ZNF224 Recruits the Arginine Methyltransferase PRMT5 on the Transcriptional Repressor Complex of the Aldolase A Gene
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DOI：
10.1074/jbc.m109.043349
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发表时间：
2009-11-20
影响因子：
4.8
通讯作者：
Costanzo, Paola
中科院分区：
文献类型：
--
作者：
Cesaro, Elena;De Cegli, Rossella;Costanzo, Paola
真核生物的基因转录是通过特定转录因子和染色质调节蛋白的协同募集来调节的。事实上，基因的激活和/或抑制是由特定精氨酸或赖氨酸残基的组蛋白甲基化状态调节的。在这项工作中，通过共免疫沉淀实验，我们证明了PRMT5，一种II型蛋白精氨酸甲基转移酶，可以单甲基化和对称二甲基化精氨酸残基，与Kruppel-like相关盒锌指蛋白ZNF224（醛缩酶a基因抑制因子）存在物理关联。此外，染色质免疫沉淀实验表明PRMT5被募集到l型醛缩酶A启动子上，并且l型启动子区域周围核小体的甲基化发生在体内组蛋白H4的精氨酸3上。与其与ZNF224抑制因子复合物的关联一致，RNA干扰导致的PRMT5表达减少积极影响l型醛缩酶A启动子转录。最后，在增殖和生长受阻的细胞中，ZNF224-PRMT5抑制复合体交替占据l型醛缩酶A启动子，这表明这些调节蛋白在人类醛缩酶A基因表达的细胞周期调节中发挥了重要作用。我们的数据代表了蛋白质精氨酸甲基化在znf224介导的转录抑制中发挥作用的第一个实验证据，并为kruppel样相关盒锌指蛋白抑制基因转录所需的染色质修饰提供了新的见解。
Gene transcription in eukaryotes is modulated by the coordinated recruitment of specific transcription factors and chromatin-modulating proteins. Indeed, gene activation and/or repression is/are regulated by histone methylation status at specific arginine or lysine residues. In this work, by co-immunoprecipitation experiments, we demonstrate that PRMT5, a type II protein arginine methyltransferase that monomethylates and symmetrically dimethylates arginine residues, is physically associated with the Kruppel-like associated box-zinc finger protein ZNF224, the aldolase A gene repressor. Moreover, chromatin immunoprecipitation assays show that PRMT5 is recruited to the L-type aldolase A promoter and that methylation of the nucleosomes that surround the L-type promoter region occurs in vivo on the arginine 3 of histone H4. Consistent with its association to the ZNF224 repressor complex, the decrease of PRMT5 expression produced by RNA interference positively affects L-type aldolase A promoter transcription. Finally, the alternating occupancy of the L-type aldolase A promoter by the ZNF224-PRMT5 repression complex in proliferating and growth-arrested cells suggests that these regulatory proteins play a significant role during the cell cycle modulation of human aldolase A gene expression. Our data represent the first experimental evidence that protein arginine methylation plays a role in ZNF224-mediated transcriptional repression and provide novel insight into the chromatin modifications required for repression of gene transcription by Kruppel-like associated box-zinc finger proteins.