MARGE is a robust methodology that leverages a comprehensive library of genome-wide H3K27ac ChIP-seq profiles to predict key regulated genes and cis-regulatory regions in human or mouse. The framework has three main functions: MARGE-potential, MARGE-express, and MARGE-cistrome.



MARGE-potential defines a regulatory potential (RP) for each gene as the sum of H3K27ac ChIP-seq signals weighted by a function of genomic distance from the transcription start site. The MARGE framework includes a compendium of RPs derived from 365 human and 267 mouse H3K27ac ChIP-seq datasets. Relative RPs, scaled using this compendium, are superior to super-enhancers in predicting BET-inhibitor repressed genes.


MARGE-express, uses regression to link gene expression perturbations with regulatory potentials derived from a small subset of H3K27ac ChIP-seq data from the full compendium. In this way MARGE determines changes in regulatory potentials that are predictive of gene expression changes. Many biological perturbations that have been profiled using microarray or RNA-seq expression analysis have not been studied using chromatin profiling techniques such as ChIP-seq or DNase-seq. MARGE-express serves to identify relationships between gene sets and cis-regulatory environments to enable the study of the cis-regulation of these gene sets. It can even predict differentially regulated genes, such as ncRNAs, that are absent from the platform used to measure gene expression.


MARGE-cistrome, to predict co-regulated sets of cis-elements. These cis-elements are predicted on the basis of 1kb H3K27ac ChIP-seq windows centered on the union of DNase-seq peaks that have been identified in a wide spectrum of cell types. MARGE-cistrome identifies patterns of perturbations in the cis-elements that are consistent with perturbations in the H3K27ac regulatory potentials identified by MARGE-express. Investigators who wish to understand how particular genes in their gene set are regulated can use MARGE-cistrome to identify candidate cisregulatory elements, even when chromatin profiling data is not available in their system.

Quick Start

Try MARGE with

H3K27ac bam file Only
Regulatory Potential Calculation
Relative Regulatory Potential Calculation
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Gene List Only.
Top10 Relevant Samples Selected from H3K27ac Library
Cis-Regulatory Prediction
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Both H3K27ac bam file and Gene List
All above steps
(Users H3K27ac samples will be used when Regression)
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Wang, S., Zang, C., ... Meyer, C. A. & Liu, X. S. (2016) Modeling cis-regulation with a compendium of genome-wide histone H3K27ac profiles. Genome Research, gr.201574.115.