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Distinct cytosine modification profiles define epithelial-to-mesenchymal cell-state transitions
Author(s) -
Min Kyung Lee,
Meredith Brown,
Owen M. Wilkins,
Diwakar R. Pattabiraman,
Brock C. Christensen
Publication year - 2022
Publication title -
epigenomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.265
H-Index - 60
eISSN - 1750-1911
pISSN - 1750-192X
DOI - 10.2217/epi-2022-0023
Subject(s) - biology , epigenetics , chromatin , cpg site , epithelial–mesenchymal transition , dna methylation , cytosine , epigenomics , 5 hydroxymethylcytosine , transition (genetics) , microbiology and biotechnology , epigenome , dna , genetics , cancer research , computational biology , gene , gene expression
Background: Epithelial-to-mesenchymal transition (EMT) is an early step in the invasion-metastasis cascade, involving progression through intermediate cell states. Due to challenges with isolating intermediate cell states, genome-wide cytosine modifications that define transition are not completely understood. Methods: The authors measured multiple DNA cytosine modification marks and chromatin accessibility across clonal populations residing in specific EMT states. Results: Clones exhibiting more intermediate EMT phenotypes demonstrated increased 5-hydroxymethylcytosine and decreased 5-methylcytosine. Open chromatin regions containing increased 5-hydroxymethylcytosine CpG loci were enriched in EMT transcription factor motifs and were associated with Rho GTPases. Conclusion: The results indicate the importance of both distinct and shared epigenetic profiles associated with EMT processes that may be targeted to prevent EMT progression.

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