Fbxl19 recruitment to CpG islands is required for Rnf20-mediated H2B mono-ubiquitination.
Fbxl19 recruitment to CpG islands is required for Rnf20-mediated H2B mono-ubiquitination.
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DOI：
10.1093/nar/gkx310
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发表时间：
2017-07-07
影响因子：
14.9
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Lee BK;Lee J;Shen W;Rhee C;Chung H;Kim J
RNF20催化的组蛋白H_2B-赖氨酸120单泛素化(H_2Bub1)与胚胎干细胞和成体干细胞的正常分化有关。然而，目前尚不清楚RNF20是如何被招募到其特定的靶染色体位点来建立H_2Bub1的。在这里，我们揭示了Fbxl19，一个含有CxxC结构域的蛋白，通过与RNF20相互作用，在CpG岛基因的启动子上促进H2Bub1。我们发现，Fbx119的上调增加了小鼠ES细胞中全局H_2Bub1的水平，而Fbx119的下调则降低了H_2Bub1的水平。我们的全基因组靶图揭示了Fbxl19在含有CpG岛的启动子上的优先占位，我们进一步发现Fbxl19的染色体结合是其靶标的H2Bub1所必需的。此外，我们揭示了FbxL19在与RNF20协同作用下对于ES细胞的正确分化是至关重要的。综上所述，我们的结果表明，Fbx119募集到CpG岛是RNF20介导的H2B单一泛素化所必需的。
Histone H2B lysine 120 mono-ubiquitination (H2Bub1) catalyzed by Rnf20 has been implicated in normal differentiation of embryonic stem (ES) and adult stem cells. However, it remains unknown how Rnf20 is recruited to its specific target chromosomal loci for the establishment of H2Bub1. Here, we reveal that Fbxl19, a CxxC domain-containing protein, promotes H2Bub1 at the promoters of CpG island-containing genes by interacting with Rnf20. We show that up-regulation of Fbxl19 increases the level of global H2Bub1 in mouse ES cells, while down-regulation of Fbxl19 reduces the level of H2Bub1. Our genome-wide target mapping unveils the preferential occupancy of Fbxl19 on CpG island-containing promoters, and we further discover that chromosomal binding of Fbxl19 is required for H2Bub1 of its targets. Moreover, we reveal that Fbxl19 is critical for proper differentiation of ES cells in collaboration with Rnf20. Altogether, our results demonstrate that Fbxl19 recruitment to CpG islands is required for Rnf20-mediated H2B mono-ubiquitination.