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. 2019 Jul 2;20(1):541.
doi: 10.1186/s12864-019-5932-6.

NUCLIZE for quantifying epigenome: generating histone modification data at single-nucleosome resolution using genuine nucleosome positions

Daoshan Zheng  1 , Justyna Trynda  1 , Zhifu Sun  2 , Zhaoyu Li  3
Affiliations

NUCLIZE for quantifying epigenome: generating histone modification data at single-nucleosome resolution using genuine nucleosome positions

Daoshan Zheng et al. BMC Genomics. .

Abstract

Background: Defining 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.

Results: To 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.

Conclusions: Single-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.

Keywords: Graph epigenome; Histone modification; NUCLIZE; Nucleosome positioning; Quantitative epigenomics.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
NUCLIZE: defining histone modification at single-nucleosome resolution. (a) Schematic view of the NUCLIZE approach for re-annotating histone modification data at single-nucleosome resolution. (b) The NUCLIZE Workflow. (c) Examples of single and multivalent histone modification signals at each nucleosome position near the TSS of a highly expressed gene, ASGR2, in HepG2 cells. Each color represents one single or multivalent histone modification mark in each nucleosome from combined analysis of all five histone marks
Fig. 2
Fig. 2
Distributions of single-nucleosome histone modification signals in the genome Relative occupancy of histone modification signals in each nucleosome with individual marks (1 Mark) and with combined marks (5 Marks) of five histone marks together in the whole genome and within ±2 kb of the TSS of genes in HepG2 cells
Fig. 3
Fig. 3
Patterns of a string of single-nucleosome histone modification signals near TSS. (a) Patterns of histone modification codes near TSS by the K-means clustering. Each color represents one single or multivalent histone modification mark in each nucleosome from combined analysis of all five histone marks shown in Fig. 1c. (b) Percentages of genes with and without histone marks from the clustering analysis in (a). (c) The top 5 canonical pathways could be regulated by genes in each cluster using Ingenuity
Fig. 4
Fig. 4
The correlation of histone modification codes with gene expression. (a) Distributions of the numbers of the trivalent histone mark “T” and all codes at the upstream (up), downstream (down), and combined both upstream and downstream (total) surrounding TSS. (b) Correlation of gene expression levels (RPKM) with the number of single and multivalent histone marks within ±2 kb of the TSS for all genes in HepG2 cells. T, H3K4me3/H3K9ac/H3K27ac; D, H3K4me3/H3K9ac; A, H3K4me3. (c) The violin plot of the expression values of all genes in each cluster. Black dots, the median expression levels. (d) The correlation between gene expression values and numbers of the trivalent histone mark “T” and all codes at the upstream, downstream, and combined both upstream and downstream (total) surrounding TSS. Gene expression values and histone counts are median values from Fig. 4c and a, respectively
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References

    1. Zhang Y, et al. Model-based analysis of ChIP-Seq (MACS) Genome Biol. 2008;9:R137. doi: 10.1186/gb-2008-9-9-r137. - DOI - PMC - PubMed
    1. Zang C, et al. A clustering approach for identification of enriched domains from histone modification ChIP-Seq data. Bioinformatics. 2009;25:1952–1958. doi: 10.1093/bioinformatics/btp340. - DOI - PMC - PubMed
    1. Heinz S, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38:576–589. doi: 10.1016/j.molcel.2010.05.004. - DOI - PMC - PubMed
    1. Li Z, et al. Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation. Cell. 2012;151:1608–1616. doi: 10.1016/j.cell.2012.11.018. - DOI - PMC - PubMed
    1. Li Z, Schug J, Tuteja G, White P, Kaestner KH. The nucleosome map of the mammalian liver. Nat Struct Mol Biol. 2011;18:742–746. doi: 10.1038/nsmb.2060. - DOI - PMC - PubMed