Guo Xiang, Tatsuoka Kay, Liu Rongxiang
GlaxoSmithKline, Bioinformatics Division 709 Swedeland Road, King of Prussia, PA 19406, USA.
Bioinformatics. 2006 Feb 15;22(4):392-9. doi: 10.1093/bioinformatics/bti823. Epub 2005 Dec 8.
In eukaryotic genomes, histone acetylation and thereafter departure from the chromatin are essential for gene transcription initiation. Because gene transcription is tightly regulated by transcription factors, there are some speculations on the cooperation of histone acetylation and transcription factor binding. However, systematic statistical analyses of this relationship on a genomic scale have not been reported.
We apply several statistical methods to explore this relationship on two recent genomic datasets: acetylation levels on 11 histone lysines and binding activities of 203 transcription factors, both in promoter regions across the yeast genome. By canonical correlation analysis, we find that a histone acetylation pattern is correlated with a certain profile of transcription factor binding in the genome. Furthermore, after clustering the genes by their acetylation levels on the 11 histone lysines, the genes within clusters show distinct transcription factor binding profiles, as discovered by principle component analysis. Even after applying fairly stringent statistical measurement, most of these clusters have transcription factors with binding activities significantly deviated from the overall genome. We conclude that in the yeast genome, there is a strong correlation between histone acetylation and transcription factor binding in the promoter regions.
在真核生物基因组中，组蛋白乙酰化以及随后从染色质上脱离对于基因转录起始至关重要。由于基因转录受到转录因子的严格调控，因此对于组蛋白乙酰化与转录因子结合之间的协同作用存在一些推测。然而，尚未有在基因组规模上对这种关系进行系统统计分析的报道。
我们应用多种统计方法在两个最新的基因组数据集上探究这种关系：酵母基因组中启动子区域内11个组蛋白赖氨酸的乙酰化水平以及203个转录因子的结合活性。通过典型相关分析，我们发现一种组蛋白乙酰化模式与基因组中特定的转录因子结合谱相关。此外，在根据11个组蛋白赖氨酸上的乙酰化水平对基因进行聚类后，通过主成分分析发现，聚类内的基因呈现出不同的转录因子结合谱。即使应用了相当严格的统计测量方法，这些聚类中的大多数都具有结合活性明显偏离整个基因组的转录因子。我们得出结论，在酵母基因组中，启动子区域内组蛋白乙酰化与转录因子结合之间存在很强的相关性。
