Inferring regulatory element landscapes and transcription factor networks from cancer methylomes

Lijing Yao, Hui Shen, Peter W. Laird, Peggy J. Farnham, Benjamin P. Berman

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Recent studies indicate that DNA methylation can be used to identify transcriptional enhancers, but no systematic approach has been developed for genome-wide identification and analysis of enhancers based on DNA methylation. We describe ELMER (Enhancer Linking by Methylation/Expression Relationships), an R-based tool that uses DNA methylation to identify enhancers and correlates enhancer state with expression of nearby genes to identify transcriptional targets. Transcription factor motif analysis of enhancers is coupled with expression analysis of transcription factors to infer upstream regulators. Using ELMER, we investigated more than 2,000 tumor samples from The Cancer Genome Atlas. We identified networks regulated by known cancer drivers such as GATA3 and FOXA1 (breast cancer), SOX17 and FOXA2 (endometrial cancer), and NFE2L2, SOX2, and TP63 (squamous cell lung cancer). We also identified novel networks with prognostic associations, including RUNX1 in kidney cancer. We propose ELMER as a powerful new paradigm for understanding the cis-regulatory interface between cancer-associated transcription factors and their functional target genes.

Original languageEnglish (US)
Article number105
JournalGenome Biology
Volume16
Issue number1
DOIs
StatePublished - May 21 2015
Externally publishedYes

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DNA Methylation
methylation
Methylation
cancer
Transcription Factors
transcription factors
DNA methylation
neoplasms
Genome
Squamous Cell Neoplasms
Neoplasms
Atlases
Kidney Neoplasms
Endometrial Neoplasms
Statistical Factor Analysis
kidney neoplasms
Lung Neoplasms
DNA
genome
Breast Neoplasms

ASJC Scopus subject areas

  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics
  • Genetics

Cite this

Inferring regulatory element landscapes and transcription factor networks from cancer methylomes. / Yao, Lijing; Shen, Hui; Laird, Peter W.; Farnham, Peggy J.; Berman, Benjamin P.

In: Genome Biology, Vol. 16, No. 1, 105, 21.05.2015.

Research output: Contribution to journalArticle

Yao, Lijing ; Shen, Hui ; Laird, Peter W. ; Farnham, Peggy J. ; Berman, Benjamin P. / Inferring regulatory element landscapes and transcription factor networks from cancer methylomes. In: Genome Biology. 2015 ; Vol. 16, No. 1.
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