A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation.
A cryptic Tudor domain links BRWD2/PHIP to COMPASS-mediated histone H3K4 methylation.
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DOI：
10.1101/gad.305201.117
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发表时间：
2017-10-01
影响因子：
10.5
通讯作者：
Shilatifard A
中科院分区：
文献类型：
--
作者：
Morgan MAJ;Rickels RA;Collings CK;He X;Cao K;Herz HM;Cozzolino KA;Abshiru NA;Marshall SA;Rendleman EJ;Sze CC;Piunti A;Kelleher NL;Savas JN;Shilatifard A
在这项研究中，Morgan等人鉴定了一种进化上保守的因子BRWD 2/PHIP，它与组蛋白H3 K4甲基化一起定位于人类细胞、小鼠胚胎干细胞和果蝇的全基因组。果蝇唯一的同源dBRWD 3的耗尽导致组蛋白H3 Lys 27乙酰化模式在增强子和启动子和基因表达的变化，这表明这些表观遗传修饰和转录之间的串扰通过BRWD家族。组蛋白H3 Lys 4（H3 K4）甲基化是在基因顺式调控序列（如启动子和增强子）处富集的染色质特征。在这里，我们确定了一个进化上保守的因子，BRWD 2/PHIP，它与组蛋白H3 K4甲基化在人类细胞，小鼠胚胎干细胞和果蝇的全基因组共定位。BRWD 2的生化分析表明与Cullin-4-RING泛素E3连接酶-4（CRL 4）复合物、核小体和染色质重塑物相关。BRWD 2/PHIP通过之前未鉴定的与皇家家族Tudor结构域相关的染色质结合模块（我们将其命名为CryptoTudor结构域）直接与H3 K4甲基化结合。使用CRISPR-Cas9基因敲除，我们证明COMPASS H3 K4甲基转移酶家族成员差异调节BRWD 2/PHIP染色质占有率。最后，我们证明，耗尽的单个果蝇同源dBRWD 3的结果在改变基因表达和异常模式的组蛋白H3 Lys 27乙酰化的增强子和启动子，这表明这些染色质的修改和转录之间的串扰通过BRWD蛋白质家族。
In this study, Morgan et al. identify an evolutionarily conserved factor, BRWD2/PHIP, that localizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, and Drosophila. Depletion of the Drosophila sole homolog dBRWD3 results in altered histone H3 Lys27 acetylation patterns at enhancers and promoters and changes in gene expression, suggesting a cross-talk between these epigenetic modifications and transcription through the BRWD family. Histone H3 Lys4 (H3K4) methylation is a chromatin feature enriched at gene cis-regulatory sequences such as promoters and enhancers. Here we identify an evolutionarily conserved factor, BRWD2/PHIP, which colocalizes with histone H3K4 methylation genome-wide in human cells, mouse embryonic stem cells, and Drosophila. Biochemical analysis of BRWD2 demonstrated an association with the Cullin-4–RING ubiquitin E3 ligase-4 (CRL4) complex, nucleosomes, and chromatin remodelers. BRWD2/PHIP binds directly to H3K4 methylation through a previously unidentified chromatin-binding module related to Royal Family Tudor domains, which we named the CryptoTudor domain. Using CRISPR–Cas9 genetic knockouts, we demonstrate that COMPASS H3K4 methyltransferase family members differentially regulate BRWD2/PHIP chromatin occupancy. Finally, we demonstrate that depletion of the single Drosophila homolog dBRWD3 results in altered gene expression and aberrant patterns of histone H3 Lys27 acetylation at enhancers and promoters, suggesting a cross-talk between these chromatin modifications and transcription through the BRWD protein family.
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影响因子：
16.8
作者：
Hu D;Garruss AS;Gao X;Morgan MA;Cook M;Smith ER;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
64.5
作者：
Duda, David M.;Borg, Laura A.;Scott, Daniel C.;Hunt, Harold W.;Hammel, Michal;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1073/pnas.1119949109
发表时间：
2012-05-01
影响因子：
11.1
作者：
De Semir, David;Nosrati, Mehdi;Kashani-Sabet, Mohammed
通讯作者：
Kashani-Sabet, Mohammed
影响因子：
56.9
作者：
Huang, Y;Fang, J;Xu, RM
通讯作者：
Xu, RM