Pan-cancer predictions of transcription factors mediating aberrant DNA methylation

Aberrant DNA methylation is a hallmark of cancer cells. However, the mechanisms underlying changes in DNA methylation remain elusive. Transcription factors initially thought to be repressed from binding by DNA methylation, have recently emerged as being able to shape DNA methylation patterns. Here,...

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Bibliographic Details
Published in:Epigenetics & chromatin 2022-03, Vol.15 (1), p.10-16, Article 10
Main Authors: Detilleux, Dylane, Spill, Yannick G, Balaramane, Delphine, Weber, Michaël, Bardet, Anaïs Flore
Format: Article
Language:English
Subjects:
Binding sites
Biochemistry, Molecular Biology
Bioinformatics
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cancer
CpG Islands
Discriminant analysis
DNA
DNA binding proteins
DNA Methylation
EGR-1 protein
Female
GATA-3 protein
Gene expression
Genes
Genetic aspects
Genomes
Genomics
Humans
Life Sciences
Lung cancer
Methylation
Prostate cancer
Transcription factors
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Summary:Aberrant DNA methylation is a hallmark of cancer cells. However, the mechanisms underlying changes in DNA methylation remain elusive. Transcription factors initially thought to be repressed from binding by DNA methylation, have recently emerged as being able to shape DNA methylation patterns. Here, we integrated the massive amount of data available from The Cancer Genome Atlas to predict transcription factors driving aberrant DNA methylation in 13 cancer types. We identified differentially methylated regions between cancer and matching healthy samples, searched for transcription factor motifs enriched in those regions and selected transcription factors with corresponding changes in gene expression. We predict transcription factors known to be involved in cancer as well as novel candidates to drive hypo-methylated regions such as FOXA1 and GATA3 in breast cancer, FOXA1 and TWIST1 in prostate cancer and NFE2L2 in lung cancer. We also predict transcription factors that lead to hyper-methylated regions upon transcription factor loss such as EGR1 in several cancer types. Finally, we validate that FOXA1 and GATA3 mediate hypo-methylated regions in breast cancer cells. Our work highlights the importance of some transcription factors as upstream regulators shaping DNA methylation patterns in cancer.
ISSN:1756-8935
1756-8935
DOI:10.1186/s13072-022-00443-w