Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability.
Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability.
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DOI：
10.1038/ng.3965
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发表时间：
2017-11
期刊：
影响因子：
30.8
通讯作者：
Shilatifard A
中科院分区：
文献类型：
--
作者：
Rickels R;Herz HM;Sze CC;Cao K;Morgan MA;Collings CK;Gause M;Takahashi YH;Wang L;Rendleman EJ;Marshall SA;Krueger A;Bartom ET;Piunti A;Smith ER;Abshiru NA;Kelleher NL;Dorsett D;Shilatifard A
组蛋白H3赖氨酸4单甲基化（H3 K4 me 1）是由Trr/MLL 3/4-COMPASS家族催化的增强子染色质的进化上保守的特征。在这里，我们表明，果蝇胚胎表达催化缺陷的Trr-COMPASS关闭和发展到一个富有成效的成年。用增强酶产物特异性的Trr等位基因进行的平行实验表明，在增强子处H3 K4 me 1转化为H3 K4 me 2和H3 K4 me 3也与生命相容，并导致基因表达的最小变化。类似地，胚胎干细胞中哺乳动物MLL 3和MLL 4催化SET结构域的缺失不会破坏ES细胞的自我更新能力。Trr催化突变等位基因表现出微妙的发育表型时，受到温度胁迫或改变的粘附素水平。总的来说，我们的研究结果表明，后生动物的发展可以发生在TRR/COMPASS与H3 K4 me 1酶缺乏的背景下，并指出H3 K4 me 1在特定环境中对顺式调控元件的可能作用，以微调转录调控响应环境压力。
Histone H3 lysine 4 monomethylation (H3K4me1) is an evolutionarily conserved feature of enhancer chromatin catalyzed by the Trr/MLL3/4-COMPASS family. Here we demonstrate that Drosophila embryos expressing catalytically deficient Trr-COMPASS eclose and develop to a productive adulthood. Parallel experiments with a Trr allele that augments enzyme product specificity reveal that conversion of H3K4me1 at enhancers to H3K4me2 and H3K4me3 is also compatible with life and results in minimal changes in gene expression. Similarly, loss of mammalian MLL3 and MLL4 catalytic SET domain in embryonic stem cells does not disrupt self-renewal capability of the ES cells. Trr catalytic mutant alleles manifest subtle developmental phenotypes when subjected to temperature stress or altered cohesin levels. Collectively, our findings suggest that metazoan development can occur in the context of Trr/COMPASS with H3K4me1 enzymatic deficiency, and points to a possible role for H3K4me1 on cis-regulatory elements in specific settings to fine-tune transcriptional regulation in response to environmental stress.
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影响因子：
64.5
作者：
Phillips-Cremins JE;Sauria ME;Sanyal A;Gerasimova TI;Lajoie BR;Bell JS;Ong CT;Hookway TA;Guo C;Sun Y;Bland MJ;Wagstaff W;Dalton S;McDevitt TC;Sen R;Dekker J;Taylor J;Corces VG
通讯作者：
Corces VG
影响因子：
5.6
作者：
Jang Y;Wang C;Zhuang L;Liu C;Ge K
通讯作者：
Ge K
影响因子：
16
作者：
Rickels R;Hu D;Collings CK;Woodfin AR;Piunti A;Mohan M;Herz HM;Kvon E;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Kanda, Hiroshi;Alexander Nguyen;Hariharan, Iswar K.
通讯作者：
Hariharan, Iswar K.