Abstract
BackgroundDefining histone modification at single-nucleosome resolution provides accurate epigenomic information in individual nucleosomes. However, most of histone modification data deposited in current databases, such as ENCODE and Roadmap, have low resolution with peaks of several kilo-base pairs (kb), which due to the technical defects of regular ChIP-Seq technology.ResultsTo generate histone modification data at single-nucleosome resolution, we developed a novel approach, NUCLIZE, using synergistic analyses of histone modification data from ChIP-Seq and high-resolution nucleosome mapping data from native MNase-Seq. With this approach, we generated quantitative epigenomics data of single and multivalent histone modification marks in each nucleosome. We found that the dominant trivalent histone mark (H3K4me3/H3K9ac/H3K27ac) and others showed defined and specific patterns near each TSS, indicating potential epigenetic codes regulating gene transcription.ConclusionsSingle-nucleosome histone modification data render epigenomic data become quantitative, which is essential for investigating dynamic changes of epigenetic regulation in the biological process or for functional epigenomics studies. Thus, NUCLIZE turns current epigenomic mapping studies into genuine functional epigenomics studies with quantitative epigenomic data.
Highlights
ResultsTo generate histone modification data at single-nucleosome resolution, we developed a novel approach, NUCLIZE, using synergistic analyses of histone modification data from ChIP-Seq and high-resolution nucleosome mapping data from native micrococcal nuclease (MNase)-Seq
Defining histone modification at single-nucleosome resolution provides accurate epigenomic information in individual nucleosomes
Intra- and cross-platform analysis using NUCLIZE Compared to large amount of histone modification mapping data that have been generated in the public databases, high-resolution nucleosome mapping has only been completed in a few human normal and cancer cell types, including CD4+ and CD8+ T-cells [8, 9], CD34+ hematopoietic stem cells and their derivatives, CD36+ erythroid lineage cells [10], IMR90 cells [11], human sperm [12, 13], human lymphoblastoid cell lines [14, 15], MCF7 [16], HEK293 [17], and K562 [15]; the qualities of these nucleosome mapping data varied and some data were from micrococcal nuclease (MNase) digestion of crosslinked chromatin
Summary
Single-nucleosome histone modification data in human cells With our approach, we obtained single-nucleosome resolution of histone modification data, including H3K4me, H3K9ac, H3K9me, H3K27ac, and H3K27me, in HepG2 cells. The principal component analysis (PCA) showed that our data of single and multivalent histone marks in each nucleosome were highly similar with both sets of ENCODE data compared to noncorrelated data from MCF7 cells (Additional file 1: Figure S3) These data indicate that our NUCLIZE approach to define histone modification data into singlenucleosome resolution is promising for the crossplatform analysis. Our high-resolution histone modification data at single-nucleosome resolution provided us a great opportunity to tackle this question by expanding it to a consecutive set of quantitative histone marks in a string of nucleosomes at gene regulatory regions To determine whether these defined numbers or lengths of single and multivalent histone marks have patterns or whether there are epigenetic codes for regulating gene expression at the genomic regulatory regions surrounding the TSS, we evaluated the histone modification codes for each gene in HepG2 cells. Epigenomics studies in dealing with large amount of mapping data for histone modification using regular ChIP-Seq that deposited in the public databases and practicable for current quantitative epigenomics studies
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