A high-resolution whole-genome map of key chromatin modifications in the adult Drosophila melanogaster.
A high-resolution whole-genome map of key chromatin modifications in the adult Drosophila melanogaster.
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DOI：
10.1371/journal.pgen.1002380
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发表时间：
2011-12
期刊：
影响因子：
4.5
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Yin H;Sweeney S;Raha D;Snyder M;Lin H
表观遗传学的研究一直集中在细胞类型特异性调节;对生物体内不同细胞类型所共有的表观遗传编程的共同特征知之甚少。在这里，我们报告了一种改进的染色质免疫沉淀和深度测序（ChIP-Seq）的方法，并使用它来构建果蝇关键组蛋白标记，异染色质蛋白1a（HP 1a）和RNA聚合酶II（polII）的高分辨率地图。这些因子在50 bp分辨率的全基因组和5 bp分辨率的基因调控序列上进行了定位，这揭示了主要成年果蝇细胞类型所共有的染色质修饰景观的基本特征：异染色质和常染色质标记在转座子和重复序列中的富集，HP 1a在转录起始位点的积累与停滞的polII，组蛋白编码和polII水平/转录起始位点周围的位置，预测mRNA水平和基因的功能，以及剪接连接处外显子内延长polII的富集。这些特征，可能在不同的表观基因组中保守，揭示了染色质修饰的一般策略。正如基因组序列图是遗传学研究不可或缺的，表观基因组图是表观遗传学研究的关键。这对于复杂的遗传模型尤其如此，如果蝇，其中关于遗传学和发育生物学的丰富信息等待在全基因组规模上进行系统的表观遗传学解释。在这份手稿中，我们报告了一个高分辨率的地图，在果蝇基因组中的关键染色质修饰的ChIP-Seq方法构建。这张地图是从成年果蝇的所有细胞类型中推导出来的，并根据它们的自然丰度进行加权。它包含关键的组蛋白标记HP 1a和RNA聚合酶II，在整个基因组中以50个碱基对的分辨率绘制，在基因调控序列中以5个碱基对的分辨率绘制。它揭示了显着的特点，染色质修饰和转录调控共享的主要成年果蝇细胞类型。我们预计，这张地图和显着的染色质修饰景观揭示了这张地图应该有广泛的用途，表观遗传学，发育生物学和干细胞生物学领域。
Epigenetic research has been focused on cell-type-specific regulation; less is known about common features of epigenetic programming shared by diverse cell types within an organism. Here, we report a modified method for chromatin immunoprecipitation and deep sequencing (ChIP–Seq) and its use to construct a high-resolution map of the Drosophila melanogaster key histone marks, heterochromatin protein 1a (HP1a) and RNA polymerase II (polII). These factors are mapped at 50-bp resolution genome-wide and at 5-bp resolution for regulatory sequences of genes, which reveals fundamental features of chromatin modification landscape shared by major adult Drosophila cell types: the enrichment of both heterochromatic and euchromatic marks in transposons and repetitive sequences, the accumulation of HP1a at transcription start sites with stalled polII, the signatures of histone code and polII level/position around the transcriptional start sites that predict both the mRNA level and functionality of genes, and the enrichment of elongating polII within exons at splicing junctions. These features, likely conserved among diverse epigenomes, reveal general strategies for chromatin modifications. Just as a genome sequence map is indispensible to genetic studies, an epigenome map is crucial for epigenetic research. This is especially true for a sophisticated genetic model such as Drosophila melanogaster, where the wealth of information on genetics and developmental biology awaits systematic epigenetic interpretation on a whole-genome scale. In this manuscript, we report a high-resolution map of key chromatin modifications in the Drosophila genome constructed by the ChIP–Seq approach. This map is derived from all cell types in the adult Drosophila weighted by their natural abundance. It contains key histone marks, HP1a and RNA polymerase II, mapped at 50-bp resolution throughout the genome and at 5-bp resolution for regulatory sequences of genes. It reveals striking features of chromatin modification and transcriptional regulation shared by major adult Drosophila cell types. We anticipate that this map and the salient chromatin modification landscapes revealed by this map should have broad utility to the fields of epigenetics, developmental biology, and stem cell biology.
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