Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.
Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.
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DOI：
10.1038/nature22822
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发表时间：
2017-07-13
期刊：
影响因子：
64.8
通讯作者：
Narlikar GJ
中科院分区：
文献类型：
--
作者：
Larson AG;Elnatan D;Keenen MM;Trnka MJ;Johnston JB;Burlingame AL;Agard DA;Redding S;Narlikar GJ
异染色质引起的基因沉默被认为部分是由于HP 1蛋白在基因组的大区域中扩散、压缩潜在的染色质和募集抑制活性的能力。在这里，我们确定了人类HP 1 α蛋白的一个新特性：形成相分离液滴的能力。虽然未修饰的HP 1 α是可溶的，但其N-末端延伸的磷酸化或DNA结合促进相分离液滴的形成。磷酸化驱动的相分离可以通过特异性HP 1 α配体促进或逆转。异染色质的已知成分如核小体和DNA优先分配到HP 1 α液滴中，但其他分子如转录因子TFIIB没有显示出优先性。使用单分子DNA幕帘，我们发现未修饰和磷酸化的HP 1 α诱导DNA链快速压缩成斑点，尽管具有不同的特征。我们通过将蛋白质直接递送到哺乳动物细胞中显示，不能在体外进行相分离的HP 1 α突变体比磷酸化的HP 1 α形成更小和更少的核斑点。这些研究结果表明，异染色质介导的基因沉默可能发生在部分通过螯合的压实染色质相分离的HP 1液滴，这是溶解或形成的特定配体的基础上核上下文。
Gene silencing by heterochromatin is proposed to occur in part from the ability of HP1 proteins to spread across large regions of the genome, compact the underlying chromatin and recruit repressive activities. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation driven phase-separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets but other molecules such as the transcription factor TFIIB show no preference. Using single-molecule DNA curtains we find that unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, though with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands based on nuclear context.
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影响因子：
19
作者：
Canzio, Daniele;Larson, Adam;Narlikar, Geeta J.
通讯作者：
Narlikar, Geeta J.
DOI：
10.1021/acs.langmuir.5b02416
发表时间：
2015-09-22
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Gallardo IF;Pasupathy P;Brown M;Manhart CM;Neikirk DP;Alani E;Finkelstein IJ
通讯作者：
Finkelstein IJ
DOI：
10.1007/s13361-015-1235-6
发表时间：
2015-12
影响因子：
3.2
作者：
Lu, Jonathan;Trnka, Michael J.;Roh, Soung-Hun;Robinson, Philip J. J.;Shiau, Carrie;Fujimori, Danica Galonic;Chiu, Wah;Burlingame, Alma L.;Guan, Shenheng
通讯作者：
Guan, Shenheng
影响因子：
64.8
作者：
Li, Pilong;Banjade, Sudeep;Cheng, Hui-Chun;Kim, Soyeon;Chen, Baoyu;Guo, Liang;Llaguno, Marc;Hollingsworth, Javoris V.;King, David S.;Banani, Salman F.;Russo, Paul S.;Jiang, Qiu-Xing;Nixon, B. Tracy;Rosen, Michael K.
通讯作者：
Rosen, Michael K.
影响因子：
3.3
作者：
Kang J;Chaudhary J;Dong H;Kim S;Brautigam CA;Yu H
通讯作者：
Yu H