KDM2B is a histone H3K79 demethylase and induces transcriptional repression via sirtuin-1-mediated chromatin silencing
KDM2B is a histone H3K79 demethylase and induces transcriptional repression via sirtuin-1-mediated chromatin silencing
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DOI：
10.1096/fj.201800242r
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发表时间：
2018-10-01
期刊：
影响因子：
4.8
通讯作者：
Seo, Sang-Beom
中科院分区：
文献类型：
--
作者：
Kang, Joo-Young;Kim, Ji-Young;Seo, Sang-Beom
组蛋白H3赖氨酸79 （H3K79）的甲基化是一个活跃的染色质标记，在基因组的活跃转录区域很突出；然而，尽管有大量的研究，H3K79的去甲基化酶仍然未知。在这里，我们发现KDM2B，也被称为FBXL10，是Jumonji C家族的一员，以其组蛋白H3K36去甲基化酶活性而知名，是二甲基和三甲基H3K79去甲基化酶。我们证明KDM2B通过占用启动子和H3K79的去甲基化诱导HOXA7和meis1的转录抑制。此外，全基因组分析表明，当KDM2B被耗尽时，H3K79甲基化水平增加，这表明KDM2B在体内发挥H3K79去甲基化酶的作用。最后，稳定的kdm2b敲低细胞系表现出染色质中NAD（+）依赖性去乙酰化酶sirtuin-1 （SIRT1）的移位，同时H3K79甲基化和H4K16乙酰化增加。我们的研究发现KDM2B是一种H3K79去甲基化酶，并通过sirt1介导的染色质沉默将其功能与转录抑制联系起来。Kang J.-Y。Kim, j - y。Kim, k - b。，朴建伟，赵洪辉，Hahm, j.y Y，蔡玉成。， Kim， D, Kook， H., lee， S., Ha, n.c。Seo, s.b。KDM2B是一种组蛋白H3K79去甲基化酶，通过sirtuin-1介导的染色质沉默诱导转录抑制。
The methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and is prominent in actively transcribed regions of the genome; however, demethylase of H3K79 remains unknown despite intensive research. Here, we show that KDM2B, also known as FBXL10 and a member of the Jumonji C family of proteins known for its histone H3K36 demethylase activity, is a di- and trimethyl H3K79 demethylase. We demonstrate that KDM2B induces transcriptional repression of HOXA7 and MEIS1via occupancy of promoters and demethylation of H3K79. Furthermore, genome-wide analysis suggests that H3K79 methylation levels increase when KDM2B is depleted, which indicates that KDM2B functions as an H3K79 demethylase in vivo. Finally, stable KDM2B-knockdown cell lines exhibit displacement of NAD(+)-dependent deacetylase sirtuin-1 (SIRT1) from chromatin, with concomitant increases in H3K79 methylation and H4K16 acetylation. Our findings identify KDM2B as an H3K79 demethylase and link its function to transcriptional repression via SIRT1-mediated chromatin silencing.Kang, J.-Y., Kim, J.-Y., Kim, K.-B., Park, J. W., Cho, H., Hahm, J. Y., Chae, Y.-C., Kim, D., Kook, H., Rhee, S., Ha, N.-C., Seo, S.-B. KDM2B is a histone H3K79 demethylase and induces transcriptional repression via sirtuin-1-mediated chromatin silencing.