Single-molecule kinetic analysis of HP1-chromatin binding reveals a dynamic network of histone modification and DNA interactions.
Single-molecule kinetic analysis of HP1-chromatin binding reveals a dynamic network of histone modification and DNA interactions.
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DOI：
10.1093/nar/gkx697
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发表时间：
2017-10-13
影响因子：
14.9
通讯作者：
Fierz B
中科院分区：
文献类型：
--
作者：
Bryan LC;Weilandt DR;Bachmann AL;Kilic S;Lechner CC;Odermatt PD;Fantner GE;Georgeon S;Hantschel O;Hatzimanikatis V;Fierz B
参与基因调控的效应蛋白的染色质募集依赖于与组蛋白翻译后修饰（PTM）的多价相互作用和染色质纤维的结构特征。由于涉及复杂的相互作用，目前还不清楚效应子如何动态地对染色质景观进行采样。在这里，我们剖析了动态染色质相互作用的一个家庭的多价效应，异染色质蛋白1（HP1）的蛋白质，使用单分子荧光成像和计算建模。我们发现，三个人类HP1亚型的招募和保留在染色质上的组蛋白PTM和DNA结合状态之间的动态交换。这些相互作用取决于局部染色质结构、HP1亚型以及HP1本身上的PTM。在HP1亚型中，由于DNA相互作用以及PTM结合，HP1α表现出最长的停留时间和最快的结合速率。HP 1 α磷酸化通过增强多价性同时减少DNA结合进一步增加染色质保留。由于在许多染色质效应物中发现DNA结合与特异性PTM识别相结合，因此我们提出了一种用于效应物招募的一般动态捕获机制。多个弱蛋白质和DNA相互作用导致多价相互作用网络，其将效应子靶向特定的染色质修饰状态，其中需要它们的活性。
Chromatin recruitment of effector proteins involved in gene regulation depends on multivalent interaction with histone post-translational modifications (PTMs) and structural features of the chromatin fiber. Due to the complex interactions involved, it is currently not understood how effectors dynamically sample the chromatin landscape. Here, we dissect the dynamic chromatin interactions of a family of multivalent effectors, heterochromatin protein 1 (HP1) proteins, using single-molecule fluorescence imaging and computational modeling. We show that the three human HP1 isoforms are recruited and retained on chromatin by a dynamic exchange between histone PTM and DNA bound states. These interactions depend on local chromatin structure, the HP1 isoforms as well as on PTMs on HP1 itself. Of the HP1 isoforms, HP1α exhibits the longest residence times and fastest binding rates due to DNA interactions in addition to PTM binding. HP1α phosphorylation further increases chromatin retention through strengthening of multivalency while reducing DNA binding. As DNA binding in combination with specific PTM recognition is found in many chromatin effectors, we propose a general dynamic capture mechanism for effector recruitment. Multiple weak protein and DNA interactions result in a multivalent interaction network that targets effectors to a specific chromatin modification state, where their activity is required.
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影响因子：
5.6
作者：
Lowary, PT;Widom, J
通讯作者：
Widom, J
影响因子：
4
作者：
Dialynas, George K.;Terjung, Stefan;Georgatos, Spyros D.
通讯作者：
Georgatos, Spyros D.
影响因子：
64.8
作者：
Larson AG;Elnatan D;Keenen MM;Trnka MJ;Johnston JB;Burlingame AL;Agard DA;Redding S;Narlikar GJ
通讯作者：
Narlikar GJ
影响因子：
64.8
作者：
Ayoub, Nabieh;Jeyasekharan, Anand D.;Venkitaraman, Ashok R.
通讯作者：
Venkitaraman, Ashok R.
影响因子：
4.8
作者：
Azzaz, Abdelhamid M.;Vitalini, Michael W.;Shogren-Knaak, Michael A.
通讯作者：
Shogren-Knaak, Michael A.