Department of Biology, Washington University St Louis, Missouri 63130, USA.
Genome Res. 2011 Feb;21(2):147-63. doi: 10.1101/gr.110098.110. Epub 2010 Dec 22.
Eukaryotic genomes are packaged in two basic forms, euchromatin and heterochromatin. We have examined the composition and organization of Drosophila melanogaster heterochromatin in different cell types using ChIP-array analysis of histone modifications and chromosomal proteins. As anticipated, the pericentric heterochromatin and chromosome 4 are on average enriched for the "silencing" marks H3K9me2, H3K9me3, HP1a, and SU(VAR)3-9, and are generally depleted for marks associated with active transcription. The locations of the euchromatin-heterochromatin borders identified by these marks are similar in animal tissues and most cell lines, although the amount of heterochromatin is variable in some cell lines. Combinatorial analysis of chromatin patterns reveals distinct profiles for euchromatin, pericentric heterochromatin, and the 4th chromosome. Both silent and active protein-coding genes in heterochromatin display complex patterns of chromosomal proteins and histone modifications; a majority of the active genes exhibit both "activation" marks (e.g., H3K4me3 and H3K36me3) and "silencing" marks (e.g., H3K9me2 and HP1a). The hallmark of active genes in heterochromatic domains appears to be a loss of H3K9 methylation at the transcription start site. We also observe complex epigenomic profiles of intergenic regions, repeated transposable element (TE) sequences, and genes in the heterochromatic extensions. An unexpectedly large fraction of sequences in the euchromatic chromosome arms exhibits a heterochromatic chromatin signature, which differs in size, position, and impact on gene expression among cell types. We conclude that patterns of heterochromatin/euchromatin packaging show greater complexity and plasticity than anticipated. This comprehensive analysis provides a foundation for future studies of gene activity and chromosomal functions that are influenced by or dependent upon heterochromatin.
常染色质和异染色质。我们使用组蛋白修饰和染色体蛋白的 ChIP-array 分析，研究了不同细胞类型中果蝇黑色素体异染色质的组成和结构。正如预期的那样，着丝粒异染色质和染色体 4 通常富含“沉默”标记 H3K9me2、H3K9me3、HP1a 和 SU(VAR)3-9，并且通常缺乏与活跃转录相关的标记。这些标记确定的常染色质-异染色质边界的位置在动物组织和大多数细胞系中相似，尽管在一些细胞系中异染色质的量是可变的。染色质模式的组合分析揭示了常染色质、着丝粒异染色质和第 4 染色体的不同特征。异染色质中的沉默和活跃的蛋白质编码基因都显示出染色体蛋白和组蛋白修饰的复杂模式；大多数活跃的基因都表现出“激活”标记（例如，H3K4me3 和 H3K36me3）和“沉默”标记（例如，H3K9me2 和 HP1a）。异染色质区域中活跃基因的标志似乎是转录起始位点处 H3K9 甲基化的丧失。我们还观察到基因间区、重复转座元件 (TE) 序列和异染色质延伸区的复杂表观基因组特征。染色体臂上的常染色质中出乎意料的大比例序列表现出异染色质染色质特征，这些特征在细胞类型之间的大小、位置和对基因表达的影响上有所不同。我们得出结论，异染色质/常染色质包装的模式比预期的更为复杂和灵活。这项全面的分析为未来研究受异染色质影响或依赖于异染色质的基因活性和染色体功能提供了基础。
