Global analysis of the relationship between JIL-1 kinase and transcription.
Global analysis of the relationship between JIL-1 kinase and transcription.
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DOI：
10.1371/journal.pgen.1001327
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发表时间：
2011-03
期刊：
影响因子：
4.5
通讯作者：
Becker PB
中科院分区：
文献类型：
--
作者：
Regnard C;Straub T;Mitterweger A;Dahlsveen IK;Fabian V;Becker PB
JIL-1是一种普遍存在的串联蛋白，对果蝇的发育起着至关重要的作用。它在确定幼虫多线染色体的去凝集结构域中的作用已经得到了很好的证实，但它在转录调控中的参与仍然存在争议。为了首次对JIL-1进行全面的分子表征，我们在果蝇细胞中构建了该激酶的高分辨率、全染色体相互作用谱，并确定了它在转录中的作用。JIL-1沿着活性基因的全长与其结合。该激酶的存在与平均转录水平或聚合酶密度不成正比。比较JIL-1与延长的RNA聚合酶和各种组蛋白修饰的相关性，提出了两种不同的靶向原则。JIL-1结合的基础水平可以被定义为与组蛋白H3在赖氨酸36的甲基化最相关，这是一个共转录的标记。H4K16的额外乙酰化定义了第二种状态，其特征是大约两倍的JIL-1水平升高，这在剂量补偿的男性X染色体上尤为突出。JIL-1在体外对组蛋白H3N末端的磷酸化与其他尾部修饰是相容的。在体内，H3在丝氨酸10处的磷酸化，以及在赖氨酸14处的乙酰化，创造了一个在JIL-1结合区富含的复合组蛋白标记。它被RNA干扰耗尽，导致男性X染色体转录的轻微但显著的减少。总之，这些结果表明，JIL-1参与了一个复杂的组蛋白修饰网络，该网络的特征是活性的、去凝集的染色质。我们推测，JIL-1的一个特殊作用可能是通过组蛋白H3在丝氨酸10处的磷酸化来加强而不是建立活性染色质的状态。
The ubiquitous tandem kinase JIL-1 is essential for Drosophila development. Its role in defining decondensed domains of larval polytene chromosomes is well established, but its involvement in transcription regulation has remained controversial. For a first comprehensive molecular characterisation of JIL-1, we generated a high-resolution, chromosome-wide interaction profile of the kinase in Drosophila cells and determined its role in transcription. JIL-1 binds active genes along their entire length. The presence of the kinase is not proportional to average transcription levels or polymerase density. Comparison of JIL-1 association with elongating RNA polymerase and a variety of histone modifications suggests two distinct targeting principles. A basal level of JIL-1 binding can be defined that correlates best with the methylation of histone H3 at lysine 36, a mark that is placed co-transcriptionally. The additional acetylation of H4K16 defines a second state characterised by approximately twofold elevated JIL-1 levels, which is particularly prominent on the dosage-compensated male X chromosome. Phosphorylation of the histone H3 N-terminus by JIL-1 in vitro is compatible with other tail modifications. In vivo, phosphorylation of H3 at serine 10, together with acetylation at lysine 14, creates a composite histone mark that is enriched at JIL-1 binding regions. Its depletion by RNA interference leads to a modest, but significant, decrease of transcription from the male X chromosome. Collectively, the results suggest that JIL-1 participates in a complex histone modification network that characterises active, decondensed chromatin. We hypothesise that one specific role of JIL-1 may be to reinforce, rather than to establish, the status of active chromatin through the phosphorylation of histone H3 at serine 10.
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