Computational inference of H3K4me3 and H3K27ac domain length

PeerJ

article

Julian Zubek¹  Michael L. Stitzel³  Duygu Ucar³  Dariusz M. Plewczynski¹ 

[1] Centre of New Technologies, University of Warsaw;Institute of Computer Science;Institute for Systems Genomics, Univeristy of Connecticut, Farmington;The Jackson Laboratory for Genomic Medicine, Farmington;Faculty of Pharmacy, Medical University of Warsaw

关键词: Epigenomics;    Epigenetics;    Broad domains;    Methylation;    Acetylation;    Domain length;   

DOI  :  10.7717/peerj.1750

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background. Recent epigenomic studies have shown that the length of a DNA region covered by an epigenetic mark is not just a byproduct of the assaying technologies and has functional implications for that locus. For example, expanded regions of DNA sequences that are marked by enhancer-specific histone modifications, such as acetylation of histone H3 lysine 27 (H3K27ac) domains coincide with cell-specific enhancers, known as super or stretch enhancers. Similarly, promoters of genes critical for cell-specific functions are marked by expanded H3K4me3 domains in the cognate cell type, and these can span DNA regions from 4–5kb up to 40–50kb in length. These expanded H3K4me3 domains are known as buffer domains or super promoters.Methods. To ask what correlates with—and potentially regulates—the length of loci marked with these two important histone marks, H3K4me3 and H3K27ac, we built Random Forest regression models. With these models, we computationally identified genomic and epigenomic patterns that are predictive for the length of these marks in seven ENCODE cell lines.Results. We found that certain epigenetic marks and transcription factors explain the variability of the length of H3K4me3 and H3K27ac marks across different cell types, which implies that the lengths of these two epigenetic marks are tightly regulated in a given cell type. Our source code for the regression models and data can be found at our GitHub page: https://github.com/zubekj/broad_peaks.Discussion. Our Random Forest based regression models enabled us to estimate the individual contribution of different epigenetic marks and protein binding patterns to the length of H3K4me3 and H3K27ac deposition patterns, therefore potentially revealing genomic signatures at cell specific regulatory elements.

【 授权许可】

CC BY