Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation
Peptidylarginine deiminase 2-catalyzed histone H3 arginine 26 citrullination facilitates estrogen receptor α target gene activation
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DOI：
10.1073/pnas.1203280109
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发表时间：
2012-08-14
影响因子：
11.1
通讯作者：
Coonrod, Scott A.
中科院分区：
文献类型：
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作者：
Zhang, Xuesen;Bolt, Michael;Coonrod, Scott A.
雌激素受体α (ER α)的辅助因子可以通过翻译后修饰靶启动子上的组蛋白尾部来调节基因活性。在这里，我们发现17 - β -雌二醇（E2）刺激ER α阳性细胞可促进组蛋白H3精氨酸26 （H3R26）在染色质上的整体瓜氨酸化。此外，我们发现H3瓜氨酸26 （H3Cit26）修饰与ER α在靶启动子雌激素反应元件周围的去致密染色质位点上共定位。令人惊讶的是，我们还发现H3R26的瓜氨酸化是由肽精氨酸脱亚胺酶（PAD） 2催化的，而不是由PAD4（它使H4R3瓜氨酸化）催化的。此外，我们发现PAD2在E2刺激后与ER - α相互作用，抑制PAD2或ER - α均可强烈抑制E2诱导的H3R26瓜氨酸化和ER - α在靶基因启动子处的募集。总的来说，我们的数据表明E2刺激诱导PAD2通过ER α募集到目标启动子，PAD2随后瓜氨酸化H3R26，导致局部染色质去浓缩和转录激活。
Cofactors for estrogen receptor alpha (ER alpha) can modulate gene activity by posttranslationally modifying histone tails at target promoters. Here, we found that stimulation of ER alpha-positive cells with 17 beta-estradiol (E2) promotes global citrullination of histone H3 arginine 26 (H3R26) on chromatin. Additionally, we found that the H3 citrulline 26 (H3Cit26) modification colocalizes with ER alpha at decondensed chromatin loci surrounding the estrogen-response elements of target promoters. Surprisingly, we also found that citrullination of H3R26 is catalyzed by peptidylarginine deiminase (PAD) 2 and not by PAD4 (which citrullinates H4R3). Further, we showed that PAD2 interacts with ER alpha after E2 stimulation and that inhibition of either PAD2 or ER alpha strongly suppresses E2-induced H3R26 citrullination and ER alpha recruitment at target gene promoters. Collectively, our data suggest that E2 stimulation induces the recruitment of PAD2 to target promoters by ER alpha, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation.