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. 2022 Apr 27;21:106. doi: 10.1186/s12943-022-01579-9

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visithttp://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — The transcriptional activation of ALDH2 is cooperatively regulated by NFYA and EHMT2. A The expression levels of epigenetic enzymes in NCI-H460 and NCI-H460/PTX cells by gene microarray analysis. B Left: Epigenetic enzymes and their corresponding inhibitors. Right: The protein expression levels of ALDH2 in NSCLC/PTX cells treated with epigenetic enzyme inhibitors. C ALDH2 protein levels in NSCLC/PTX cells treated with EHMT2 inhibitors (UNC0638, UNC0642, UNC0631) and a JMJD inhibitor (JIB04). D-E Luciferase activity elicited by the ALDH2 P1 promotor in NSCLC/PTX cells after overexpression of NFYA or treatment with epigenetic enzyme inhibitors. ^**p < 0.01, ^***p < 0.001, as compared to the promotor group. ^##p < 0.01, ^###p < 0.001, as compared to the NFYA overexpression group. F Left: ChIP-Seq summary plot of H3K9me2-binding intensities across H3K9me2 peaks in NCI-H460 and NCI-H460/PTX cells. Right: ChIP-Seq summary plot of Ac-H3-binding intensities across Ac-H3 peaks in NCI-H460 and NCI-H460/PTX cells. G Top: ChIP assay for the H3K9me2 modification involved in ALDH2 in NCI-H460 and NCI-H460/PTX cells. Middle: ChIP assay for the Ac-H3 modification involved in ALDH2 in NCI-H460 and NCI-H460/PTX cells. Bottom: ChIP assay for the NFYA modification involved in ALDH2 in NCI-H460 cells. ^**p < 0.01, ^***p < 0.001, as compared to the control group