Epigenetic Conservation Is a Beacon of Function: An Analysis Using Methcon5 Software for Studying Gene Methylation

Author:

Hvitfeldt Emil1,Xia Chao1,Siegmund Kimberly D.1,Shibata Darryl2,Marjoram Paul1

Affiliation:

1. Biostatistics Division, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA

2. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA

Abstract

PURPOSE Different epigenetic configurations allow one genome to develop into multiple cell types. Although the rules governing what epigenetic features confer gene expression are increasingly being understood, much remains uncertain. Here, we used a novel software package, Methcon5, to explore whether the principle of biologic conservation can be used to identify expressed genes. The hypothesis is that epigenetic configurations of important expressed genes will be conserved within a tissue. MATERIALS AND METHODS We compared the DNA methylation of approximately 850,000 CpG sites between multiple clonal crypts or glands of human colon, small intestine, and endometrium. We performed this analysis using the new software package, Methcon5, which enables detection of regions of high (or low) conservation. RESULTS We showed that DNA methylation is preferentially conserved at gene-associated CpG sites, particularly in gene promoters (eg, near the transcription start site) or the first exon. Furthermore, higher conservation correlated well with gene expression levels and performed better than promoter DNA methylation levels. Most conserved genes are in canonical housekeeping pathways. CONCLUSION This study introduces the new software package, Methcon5. In this example application, we showed that epigenetic conservation provides an alternative method for identifying functional genomic regions in human tissues.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

General Medicine

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