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
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
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
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.
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.
PMID:27466232
