Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells
Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells
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DOI：
10.1038/ncb1413
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发表时间：
2006-06-01
影响因子：
21.3
通讯作者：
Surani, M. Azim
中科院分区：
文献类型：
--
作者：
Ancelin, Katia;Lange, Ulrike C.;Surani, M. Azim
Blimp 1是一种转录抑制因子，在胚胎第7.5天（E7.5）小鼠原始生殖细胞（PGCs）的特化中起着至关重要的作用（1，2）。该SET-PR结构域蛋白可以以上下文依赖性方式与各种染色质修饰剂形成复合物（3，4）。在这里，我们表明，Blimp 1有一个新的相互作用与Prmt 5，精氨酸特异性组蛋白甲基转移酶，介导对称二甲基化的精氨酸3组蛋白H2 A和/或H4的尾巴（H2 A/H4 R3 me 2s）。Prmt 5已被证明与果蝇（Drosophila melanogaster 5）的种质组分Tudor相关。Blimp 1-Prmt 5共定位导致E8.5时PGCs中高水平的H2 A/H4 R3甲基化。然而，在E11.5，Blimp 1-Prmt 5从细胞核易位到细胞质，导致在生殖细胞广泛的表观遗传重编程时H2 A/H4 R3甲基化的丧失（6）。随后，Blimp 1-Prmt 5复合物的推定靶标Dhx 38被上调。有趣的是，当Blimp 1表达丢失时，Dhx 38的表达也见于来源于PGCs的多能胚胎生殖细胞中。我们的研究表明，Blimp 1参与了小鼠生殖细胞谱系中的一种新型转录调控复合物。
Blimp1, a transcriptional repressor, has a crucial role in the specification of primordial germ cells (PGCs) in mice at embryonic day 7.5 (E7.5)(1,2). This SET-PR domain protein can form complexes with various chromatin modifiers in a context-dependent manner(3,4). Here, we show that Blimp1 has a novel interaction with Prmt5, an arginine-specific histone methyltransferase, which mediates symmetrical dimethylation of arginine 3 on histone H2A and/or H4 tails (H2A/H4R3me2s). Prmt5 has been shown to associate with Tudor, a component of germ plasm in Drosophila melanogaster5. Blimp1-Prmt5 colocalization results in high levels of H2A/H4 R3 methylation in PGCs at E8.5. However, at E11.5, Blimp1-Prmt5 translocates from the nucleus to the cytoplasm, resulting in the loss of H2A/H4 R3 methylation at the time of extensive epigenetic reprogramming of germ cells(6). Subsequently, Dhx38, a putative target of the Blimp1-Prmt5 complex, is upregulated. Interestingly, expression of Dhx38 is also seen in pluripotent embryonic germ cells that are derived from PGCs when Blimp1 expression is lost. Our study demonstrates that Blimp1 is involved in a novel transcriptional regulatory complex in the mouse germ-cell lineage.