Jmjd3 contributes to the control of gene expression in LPS-activated macrophages.
Jmjd3 contributes to the control of gene expression in LPS-activated macrophages.
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DOI：
10.1038/emboj.2009.271
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发表时间：
2009-11-04
期刊：
影响因子：
11.4
通讯作者：
Natoli, Gioacchino
中科院分区：
文献类型：
--
作者：
De Santa, Francesca;Narang, Vipin;Yap, Zhei Hwee;Tusi, Betsabeh Khoramian;Burgold, Thomas;Austenaa, Liv;Bucci, Gabriele;Caganova, Marieta;Notarbartolo, Samuele;Casola, Stefano;Testa, Giuseppe;Sung, Wing-Kin;Wei, Chia-Lin;Natoli, Gioacchino
Jmjd 3是一种JmjC家族的组蛋白去甲基化酶，在微生物刺激下由转录因子NF-κ B诱导。Jmjd 3擦除H3 K27 me 3，一种与转录抑制相关并参与谱系决定的组蛋白标记。然而，Jmjd 3诱导和H3 K27 me 3去甲基化对炎症基因表达的具体贡献仍然未知。使用染色质免疫沉淀测序，我们发现，Jmjd 3优先招募到转录起始位点，其特征在于高水平的H3 K4 me 3，基因活性的标志物，和RNA聚合酶II（Pol_II）。此外，70%的脂多糖（LPS）诱导基因被发现是Jmjd 3的目标。尽管大多数Jmjd 3靶基因不受其缺失的影响，但包括诱导性炎症基因在内的几百个基因显示出中度受损的Pol_II募集和转录。重要的是，大多数Jmjd 3靶基因与H3 K27 me 3的可检测水平无关，并且在分析的时间窗口中Jmjd 3缺失的转录效应与对该组蛋白标记的可测量效应解耦。这些数据显示Jmjd 3以H3 K27去甲基化非依赖性方式微调LPS激活的巨噬细胞的转录输出。
Jmjd3, a JmjC family histone demethylase, is induced by the transcription factor NF-kB in response to microbial stimuli. Jmjd3 erases H3K27me3, a histone mark associated with transcriptional repression and involved in lineage determination. However, the specific contribution of Jmjd3 induction and H3K27me3 demethylation to inflammatory gene expression remains unknown. Using chromatin immunoprecipitation-sequencing we found that Jmjd3 is preferentially recruited to transcription start sites characterized by high levels of H3K4me3, a marker of gene activity, and RNA polymerase II (Pol_II). Moreover, 70% of lipopolysaccharide (LPS)-inducible genes were found to be Jmjd3 targets. Although most Jmjd3 target genes were unaffected by its deletion, a few hundred genes, including inducible inflammatory genes, showed moderately impaired Pol_II recruitment and transcription. Importantly, most Jmjd3 target genes were not associated with detectable levels of H3K27me3, and transcriptional effects of Jmjd3 absence in the window of time analysed were uncoupled from measurable effects on this histone mark. These data show that Jmjd3 fine-tunes the transcriptional output of LPS-activated macrophages in an H3K27 demethylation-independent manner.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
4.9
作者：
Ivashkiv LB;Hu X
通讯作者：
Hu X
影响因子：
64.8
作者：
Jepsen, Kristen;Solum, Derek;Rosenfeld, Michael G.
通讯作者：
Rosenfeld, Michael G.
影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
64.8
作者：
Foster, Simmie L.;Hargreaves, Diana C.;Medzhitov, Ruslan
通讯作者：
Medzhitov, Ruslan