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PHF13 通过表观遗传激活 TGFβ 驱动的上皮间质转化。

PHF13 epigenetically activates TGFβ driven epithelial to mesenchymal transition.

机构信息

The Precise Medicine Center, Department of Basic Medical College, Shenyang Medical College, Shenyang, 110034, China.

School of Pharmacy, Shenyang Medical College, Shenyang, 110034, China.

出版信息

Cell Death Dis. 2022 May 21;13(5):487. doi: 10.1038/s41419-022-04940-4.

DOI:10.1038/s41419-022-04940-4
PMID:35597793
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9124206/
Abstract

Epigenetic alteration is a pivotal factor in tumor metastasis. PHD finger protein 13 (PHF13) is a recently identified epigenetic reader of H3K4me2/3 that functions as a transcriptional co-regulator. In this study, we demonstrate that PHF13 is required for pancreatic-cancer-cell growth and metastasis. Integrative analysis of transcriptome and epigenetic profiles provide further mechanistic insights into the epigenetic regulation of genes associated with cell metastasis during the epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor β (TGFβ). Our data suggest PHF13 depletion impairs activation of TGFβ stimulated genes and correlates with a loss of active epigenetic marks (H3K4me3 and H3K27ac) at these genomic regions. These observations argue for a dependency of TGFβ target activation on PHF13. Furthermore, PHF13-dependent chromatin regions are enriched in broad H3K4me3 domains and super-enhancers, which control genes critical to cancer-cell migration and invasion, such as SNAI1 and SOX9. Overall, our data indicate a functional and mechanistic correlation between PHF13 and EMT.

摘要

表观遗传改变是肿瘤转移的关键因素。PHD 手指蛋白 13（PHF13）是最近发现的 H3K4me2/3 的表观遗传阅读器，作为转录共调节剂发挥作用。在这项研究中，我们证明 PHF13 是胰腺癌细胞生长和转移所必需的。转录组和表观遗传谱的综合分析进一步深入了解了转化生长因子β（TGFβ）诱导的上皮-间充质转化（EMT）过程中与细胞转移相关的基因的表观遗传调控。我们的数据表明，PHF13 耗竭会损害 TGFβ 刺激基因的激活，并与这些基因组区域中活性表观遗传标记（H3K4me3 和 H3K27ac）的丢失相关。这些观察结果表明 TGFβ 靶基因的激活依赖于 PHF13。此外，依赖 PHF13 的染色质区域富含广泛的 H3K4me3 结构域和超级增强子，这些区域控制着对癌细胞迁移和侵袭至关重要的基因，如 SNAI1 和 SOX9。总体而言，我们的数据表明 PHF13 与 EMT 之间存在功能和机制相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/f7ad08753bec/41419_2022_4940_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/5183875c840a/41419_2022_4940_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/ab14a50aa566/41419_2022_4940_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/6f6e17bf5080/41419_2022_4940_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/3be3d4687d24/41419_2022_4940_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/f1e4c463fe02/41419_2022_4940_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/f7ad08753bec/41419_2022_4940_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/5183875c840a/41419_2022_4940_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/48729e66cc96/41419_2022_4940_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/ab14a50aa566/41419_2022_4940_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/6f6e17bf5080/41419_2022_4940_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/3be3d4687d24/41419_2022_4940_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/f1e4c463fe02/41419_2022_4940_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68f6/9124206/f7ad08753bec/41419_2022_4940_Fig7_HTML.jpg

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