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Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29
Epithelial to mesenchymal transition (EMT) is a key trans-differentiation process, which plays a critical role in physiology and pathology. Although gene expression changes in EMT have been scrutinized, study of epigenome is in its infancy. To understand epigenetic changes during TWIST-driven EMT, w...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716732/ https://www.ncbi.nlm.nih.gov/pubmed/29228692 http://dx.doi.org/10.18632/oncotarget.21681 |
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author | Choi, Sung Kyung Pandiyan, Kurinji Eun, Jung Woo Yang, Xiaojing Hong, Seong Hwi Nam, Suk Woo Jones, Peter A. Liang, Gangning You, Jueng Soo |
author_facet | Choi, Sung Kyung Pandiyan, Kurinji Eun, Jung Woo Yang, Xiaojing Hong, Seong Hwi Nam, Suk Woo Jones, Peter A. Liang, Gangning You, Jueng Soo |
author_sort | Choi, Sung Kyung |
collection | PubMed |
description | Epithelial to mesenchymal transition (EMT) is a key trans-differentiation process, which plays a critical role in physiology and pathology. Although gene expression changes in EMT have been scrutinized, study of epigenome is in its infancy. To understand epigenetic changes during TWIST-driven EMT, we used the AcceSssIble assay to study DNA methylation and chromatin accessibility in human mammary epithelial cells (HMECs). The DNA methylation changes were found to have functional significance in EMT – i.e. methylated genes were enriched for E-box motifs that can be recognized by TWIST, at the promoters suggesting a potential targeting phenomenon, whereas the demethylated regions were enriched for pro-metastatic genes, supporting the role of EMT in metastasis. TWIST-induced EMT triggers alterations in chromatin accessibility both independent of and dependent on DNA methylation changes, primarily resulting in closed chromatin conformation. By overlapping the genes, whose chromatin structure is changed during early EMT and a known “core EMT signature”, we identified 18 driver candidate genes during EMT, 14 upregulated and 4 downregulated genes with corresponding chromatin structure changes. Among 18 genes, we focused on TRIM29 as a novel marker of EMT. Although loss of TRIM29 is insufficient to suppress CDH, it is enough to induce CDH2 and VIM. Gene functional annotation analysis shows the involvement of TRIM29 in epidermal development, cell differentiation and cell migration. Taken together, our results provide a robust snapshot of chromatin state during human EMT and identify TRIM29 as a core mediator of EMT. |
format | Online Article Text |
id | pubmed-5716732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57167322017-12-08 Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29 Choi, Sung Kyung Pandiyan, Kurinji Eun, Jung Woo Yang, Xiaojing Hong, Seong Hwi Nam, Suk Woo Jones, Peter A. Liang, Gangning You, Jueng Soo Oncotarget Research Paper Epithelial to mesenchymal transition (EMT) is a key trans-differentiation process, which plays a critical role in physiology and pathology. Although gene expression changes in EMT have been scrutinized, study of epigenome is in its infancy. To understand epigenetic changes during TWIST-driven EMT, we used the AcceSssIble assay to study DNA methylation and chromatin accessibility in human mammary epithelial cells (HMECs). The DNA methylation changes were found to have functional significance in EMT – i.e. methylated genes were enriched for E-box motifs that can be recognized by TWIST, at the promoters suggesting a potential targeting phenomenon, whereas the demethylated regions were enriched for pro-metastatic genes, supporting the role of EMT in metastasis. TWIST-induced EMT triggers alterations in chromatin accessibility both independent of and dependent on DNA methylation changes, primarily resulting in closed chromatin conformation. By overlapping the genes, whose chromatin structure is changed during early EMT and a known “core EMT signature”, we identified 18 driver candidate genes during EMT, 14 upregulated and 4 downregulated genes with corresponding chromatin structure changes. Among 18 genes, we focused on TRIM29 as a novel marker of EMT. Although loss of TRIM29 is insufficient to suppress CDH, it is enough to induce CDH2 and VIM. Gene functional annotation analysis shows the involvement of TRIM29 in epidermal development, cell differentiation and cell migration. Taken together, our results provide a robust snapshot of chromatin state during human EMT and identify TRIM29 as a core mediator of EMT. Impact Journals LLC 2017-10-09 /pmc/articles/PMC5716732/ /pubmed/29228692 http://dx.doi.org/10.18632/oncotarget.21681 Text en Copyright: © 2017 Choi et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Choi, Sung Kyung Pandiyan, Kurinji Eun, Jung Woo Yang, Xiaojing Hong, Seong Hwi Nam, Suk Woo Jones, Peter A. Liang, Gangning You, Jueng Soo Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29 |
title | Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29 |
title_full | Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29 |
title_fullStr | Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29 |
title_full_unstemmed | Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29 |
title_short | Epigenetic landscape change analysis during human EMT sheds light on a key EMT mediator TRIM29 |
title_sort | epigenetic landscape change analysis during human emt sheds light on a key emt mediator trim29 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716732/ https://www.ncbi.nlm.nih.gov/pubmed/29228692 http://dx.doi.org/10.18632/oncotarget.21681 |
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