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. 2021 Sep 6;40(42):6093–6102. doi: 10.1038/s41388-021-02001-2

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© The Author(s) 2021

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — A Circos plots of ATAC-Seq experiments with inducible MLL-AF4, inducible AF4-MLL, or the combination of constitutive MLL-AF4 in combination with inducible AF4-MLL reveal that the combination of constitutive MLL-AF4 and 48 h AF4-MLL demonstrated again the long-term impact on chromatin of this particular combination. Inducible transgenes were expressed only for 48 h and analyzed on day 3 and day 28 (inducible transgenes shut down for 25 days). B Analysis of de novo genes and shut-down genes by the DAGE/ST module. Several thousand genes were found to be induced or completely repressed by the expression of the tested t(4;11) fusion proteins. These signatures obtained at the individual timepoints were traced during the 4 weeks of the experiment and displayed by different colors (day 0 signature = blue; day 3 signature = green; day 12 signature = red; day 28 signature is orange). These analyses revealed a clonal evolutionary process that could very likely have been triggered by the expression of AF4-MLL on days 1–3.