Distinct cytosine modification profiles define epithelial-to-mesenchymal cell-state transitions

不同的胞嘧啶修饰谱决定上皮细胞到间充质细胞状态的转变

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作者:Min Kyung Lee, Meredith S Brown, Owen M Wilkins, Diwakar R Pattabiraman, Brock C Christensen

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.

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.

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.

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