ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference.
ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference.
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ISWI染色质重塑器感知核小体修饰以确定底物偏好。
DOI：
10.1038/nature23671
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发表时间：
2017-08-31
期刊：
影响因子：
64.8
通讯作者：
Muir TW
中科院分区：
文献类型：
--
作者：
Dann GP;Liszczak GP;Bagert JD;Müller MM;Nguyen UTT;Wojcik F;Brown ZZ;Bos J;Panchenko T;Pihl R;Pollock SB;Diehl KL;Allis CD;Muir TW
atp依赖的染色质重塑物通过控制体内核小体的位置来调节遗传信息的获取。然而，重塑剂区分不同核小体底物的机制尚不清楚。许多染色质重塑蛋白具有与核小体特征相互作用的保守蛋白结构域。在这里，我们使用了一种定量的高通量方法，基于dna条形码单核小体文库的使用，来分析人类ISWI家族重塑者对各种核小体修饰的生化活性。我们发现ISWI重塑剂的附属（非atp酶）亚基可以区分不同修饰的核小体，根据它们的修饰状态将重塑活性导向特定的核小体底物。出乎意料的是，我们发现核小体酸性斑块对于所有被评估的ISWI重塑剂的最大活性是必要的。这种依赖性也延伸到冠心病和SWI/SNF家族重构，这表明酸性斑块可能通常是染色质重构所必需的。至关重要的是，重塑活性可以通过酸性斑块附近的修饰来调节，这表明它可能作为atp依赖性染色质重塑者的可调相互作用热点，并且通过扩展，许多其他染色质效应物参与核小体表面的这一区域。
ATP-dependent chromatin remodellers regulate access to genetic information by controlling nucleosome positions in vivo. However, the mechanism by which remodellers discriminate between different nucleosome substrates is poorly understood. Many chromatin remodelling proteins possess conserved protein domains that interact with nucleosomal features. Here we used a quantitative high-throughput approach, based on the use of a DNA-barcoded mononucleosome library, to profile the biochemical activity of human ISWI family remodellers in response to a diverse set of nucleosome modifications. We show that accessory (non-ATPase) subunits of ISWI remodellers can distinguish between differentially modified nucleosomes, directing remodelling activity towards specific nucleosome substrates according to their modification state. Unexpectedly, we show that the nucleosome acidic patch is necessary for maximum activity of all ISWI remodellers evaluated. This dependence also extends to CHD and SWI/SNF family remodellers, suggesting that the acidic patch may be generally required for chromatin remodelling. Critically, remodelling activity can be regulated by modifications neighbouring the acidic patch, signifying that it may act as a tunable interaction hotspot for ATP-dependent chromatin remodellers and, by extension, many other chromatin effectors that engage this region of the nucleosome surface.
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影响因子：
5.6
作者：
Flaus, A;Richmond, TJ
通讯作者：
Richmond, TJ
影响因子：
2.1
作者：
Biron, E;Chatterjee, J;Kessler, H
通讯作者：
Kessler, H
DOI：
10.1126/science.1235532
发表时间：
2013-05-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kato H;Jiang J;Zhou BR;Rozendaal M;Feng H;Ghirlando R;Xiao TS;Straight AF;Bai Y
通讯作者：
Bai Y
DOI：
10.1073/pnas.1312925110
发表时间：
2013-09-10
影响因子：
11.1
作者：
Casadio, Fabio;Lu, Xiangdong;Allis, C. David
通讯作者：
Allis, C. David
影响因子：
14.9
作者：
Clapier, CR;Nightingale, KP;Becker, PB
通讯作者：
Becker, PB