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BMC Genomics  2011 

Tight associations between transcription promoter type and epigenetic variation in histone positioning and modification

DOI: 10.1186/1471-2164-12-416

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Here, we performed a systematic analysis of transcription promoters and gene expression, as well as of epigenetic histone behaviors, including genomic position, stability within the chromatin, and several modifications. We found that, in humans, broad promoters, but not peak promoters, generally had significant associations with nucleosome positioning and modification. Specifically, around broad promoters histones were highly distributed and aligned in an orderly fashion. This feature was more evident with histones that were methylated or acetylated; moreover, the nucleosome positions around the broad promoters were more stable than those around the peak ones. More strikingly, the overall expression levels of genes associated with broad promoters (but not peak promoters) with modified histones were significantly higher than the levels of genes associated with broad promoters with unmodified histones.These results shed light on how epigenetic regulatory networks of histone modifications are associated with promoter architecture.Recent progress in high-throughput technologies has made it possible to collect a variety of "omics" data on transcripts and on the epigenetic behaviors of the histones that are often associated with these transcripts [1-5].Cap analysis of gene expression (CAGE) is a high-throughput method that enables large-scale identification of transcription start sites (TSSs) of eukaryotic species. This method measures gene expression levels simultaneously with TSS identification by counting the sequenced 5' ends of full-length cDNAs, termed CAGE tags [2,6]. With the development of deep sequencing methods, more high-throughput, and high resolution "tag depth" measurements have become available (DeepCAGE, nanoCAGE and CAGEscan) [1,7]. Such recent whole-cell-level pictures of quantitative transcriptomes have revealed the complex transcriptional network of mammalian species [1,2,6]. According to recent CAGE-based analyses of human TSSs, the human "promotome"


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