Genome-wide search for Zelda-like chromatin signatures identifies GAF as a pioneer factor in early fly development
Genome-wide search for Zelda-like chromatin signatures identifies GAF as a pioneer factor in early fly development
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DOI：
10.1186/s13072-017-0141-5
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发表时间：
2017-07-04
影响因子：
3.9
通讯作者：
Kaplan, Tommy
中科院分区：
文献类型：
--
作者：
Moshe, Arbel;Kaplan, Tommy
背景资料：Zelda蛋白在果蝇的早期发育中起着关键作用，在母合子转换（MZT）之前结合数千个启动子和增强子，并标记它们的转录激活。最近，我们发现塞尔达通过组蛋白修饰的特定染色质模式来标记发育增强子和活性启动子。有趣的是，一些塞尔达位点在缺乏母体塞尔达蛋白的果蝇胚胎中仍然保持着这些染色质模式。这表明，额外的塞尔达一样的先驱因素可能会在早期的苍蝇embryo.Results：我们开发了一种计算方法来分析和完善周围的染色质景观早期塞尔达峰，使用多通道光谱聚类。这使我们能够通过MZT（有丝分裂周期8-14）表征其染色质模式。具体来说，我们专注于H3 K4 me 1，H3 K4 me 3，H3 K18 ac，H3 K27 ac和H3 K27 me 3，并确定了三种不同类型的染色质特征，匹配“启动子”，“增强子”和“瞬时结合”塞尔达峰。然后，我们使用这些染色质模式进一步扫描基因组，并确定了其他没有塞尔达结合的位点，这些位点显示出相似的染色质模式，从而产生了数百个塞尔达独立的推定增强子。发现这些区域富含GAGA因子（GAF，Trl），并且通常位于早期发育合子基因附近。总的来说，我们的分析表明，GAF，与塞尔达，在激活合子genome.Conclusions中起着重要的作用：正如我们所示，我们的计算方法提供了一个有效的算法，用于表征周围的一些感兴趣的基因座的染色质签名，并允许一个全基因组范围内的识别具有类似的染色质模式的其他基因座。
Background: The protein Zelda was shown to play a key role in early Drosophila development, binding thousands of promoters and enhancers prior to maternal-to-zygotic transition (MZT), and marking them for transcriptional activation. Recently, we showed that Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters. Intriguingly, some Zelda sites still maintain these chromatin patterns in Drosophila embryos lacking maternal Zelda protein. This suggests that additional Zelda-like pioneer factors may act in early fly embryos.Results: We developed a computational method to analyze and refine the chromatin landscape surrounding early Zelda peaks, using a multichannel spectral clustering. This allowed us to characterize their chromatin patterns through MZT (mitotic cycles 8-14). Specifically, we focused on H3K4me1, H3K4me3, H3K18ac, H3K27ac, and H3K27me3 and identified three different classes of chromatin signatures, matching "promoters," "enhancers" and " transiently bound" Zelda peaks. We then further scanned the genome using these chromatin patterns and identified additional lociwith no Zelda binding-that show similar chromatin patterns, resulting with hundreds of Zelda-independent putative enhancers. These regions were found to be enriched with GAGA factor (GAF, Trl) and are typically located near early developmental zygotic genes. Overall our analysis suggests that GAF, together with Zelda, plays an important role in activating the zygotic genome.Conclusions: As we show, our computational approach offers an efficient algorithm for characterizing chromatin signatures around some loci of interest and allows a genome-wide identification of additional loci with similar chromatin patterns.