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EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression Via Upregulating KLLN

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Journal Adv Sci (Weinh)
Date 2023 Nov 28
PMID 38015024
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Abstract

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.

Citing Articles

Insights into the mechanisms driven by H3K4 KMTs in pancreatic cancer.

LaRue-Nolan K, Raja Arul G, Sigafoos A, Shi J, Fernandez-Zapico M Biochem J. 2024; 481(15):983-997.

PMID: 39078225 PMC: 11332384. DOI: 10.1042/BCJ20230374.


EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.

Yao B, Xing M, Meng S, Li S, Zhou J, Zhang M Adv Sci (Weinh). 2023; 11(2):e2302037.

PMID: 38015024 PMC: 10787067. DOI: 10.1002/advs.202302037.

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