EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH..
Mono-methylation of histone H3 on Lys 4 (H3K4me1), which is catalyzed by histone-lysine N-methyltransferase 2D (KMT2D), serves as an important epigenetic regulator in transcriptional control. In this study, the authors identify early B-cell factor 2 (EBF2) as a binding protein of H3K4me1. Combining analyses of RNA-seq and ChIP-seq data, the authors further identify killin (KLLN) as a transcriptional target of KMT2D and EBF2 in pancreatic ductal adenocarcinoma (PDAC) cells. KMT2D-dependent H3K4me1 and EBF2 are predominantly over-lapped proximal to the transcription start site (TSS) of KLLN gene. Comprehensive functional assays show that KMT2D and EBF2 cooperatively inhibit PDAC cells proliferation, migration, and invasion through upregulating KLLN. Such inhibition on PDAC progression is also achieved through increasing H3K4me1 level by GSK-LSD1, a selective inhibitor of lysine-specific demethylase 1 (LSD1). Taken together, these findings reveal a new mechanism underlying PDAC progression and provide potential therapeutic targets for PDAC treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 11(2024), 2 vom: 01. Jan., Seite e2302037 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yao, Bing [VerfasserIn] |
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| Links: |
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| Themen: |
EBF2 |
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| Anmerkungen: |
Date Completed 27.01.2024 Date Revised 27.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/advs.202302037 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Mono-methylation of histone H3 on Lys 4 (H3K4me1), which is catalyzed by histone-lysine N-methyltransferase 2D (KMT2D), serves as an important epigenetic regulator in transcriptional control. In this study, the authors identify early B-cell factor 2 (EBF2) as a binding protein of H3K4me1. Combining analyses of RNA-seq and ChIP-seq data, the authors further identify killin (KLLN) as a transcriptional target of KMT2D and EBF2 in pancreatic ductal adenocarcinoma (PDAC) cells. KMT2D-dependent H3K4me1 and EBF2 are predominantly over-lapped proximal to the transcription start site (TSS) of KLLN gene. Comprehensive functional assays show that KMT2D and EBF2 cooperatively inhibit PDAC cells proliferation, migration, and invasion through upregulating KLLN. Such inhibition on PDAC progression is also achieved through increasing H3K4me1 level by GSK-LSD1, a selective inhibitor of lysine-specific demethylase 1 (LSD1). Taken together, these findings reveal a new mechanism underlying PDAC progression and provide potential therapeutic targets for PDAC treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EBF2 | |
| 650 | 4 | |a H3K4me1 | |
| 650 | 4 | |a KLLN | |
| 650 | 4 | |a KMT2D | |
| 650 | 4 | |a pancreatic cancer | |
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| 700 | 1 | |a Xing, Mengying |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Shixin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jingwan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Yucui |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Hongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zen, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Changyan |e verfasserin |4 aut | |
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