Motif analysis in DNAse hypersensitivity regions uncovers distal cis elements associated with gene expression



Mark Ziemann1, 2*, Antony Kaspi1, 2, Ross Lazarus5 & Assam El-Osta1, 2, 3, 4



1Epigenetics in Human Health and Disease Laboratory; 2Epigenomics Profiling Facility, Baker IDI Heart & Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia; 3Department of Pathology, The University of Melbourne, Victoria 3010, Australia; 4Central Clinical School, Department of Medicine, Monash University, Victoria 3800, Australia; 5Medical Bioinformatics, Baker IDI Heart & Diabetes Institute.


Email; *Corresponding author


Article Type

Bioinformatics Program



Received January 22, 2013; Accepted January 29, 2013; Published February 21, 2013



Reliable identification of cis regulatory elements influencing transcription remains a challenging problem in molecular bioinformatics. This is especially true for enhancer elements which are often located hundreds of kilobases from the gene promoter. High resolution DNase hypersensitivity and connectivity profiling by the ENCODE consortium provides evidence of millions of interacting cis-acting elements in the human genome. This prior knowledge can be incorporated into genome-wide expression analyses, in the form of gene sets sharing regulatory sequence motifs in known DNase hypersensitivity peak regions. High proportions of enrichment among the most extreme differentially transcribed genes from controlled biological experiments may suggest novel hypotheses about signalling pathways. The utility of this approach is demonstrated with the reanalysis of a microarray-derived gene expression data set through the Gene Set Enrichment Analysis pipeline, uncovering new putative distal cis elements in the context of innate immunity. The DNase Hypersensitivity Connectivity informed Motif Enrichment in Gene Expression (DHC-MEGE) method described here has the advantage of identifying distal elements such as enhancers, which are often overlooked with standard promoter motif analysis.



The DHC-MEGE shell script can be obtained from Sourceforge ( and the generated GMT file is attached as supplementary data.



DNAse hypersensitivity, motif enrichment, gene expression, enhancer, gene set enrichment analysis.



Ziemann et al.  Bioinformation 9(4): 212-215 (2013)


Edited by

P Kangueane






Biomedical Informatics



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