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In this study, the influence of MAPK3 on CTCF-mediated chromatin interactions in AML was examined, focusing on gene regulation and chromatin architecture. Immunoprecipitation coupled with mass spectrometry (IP-MS) was conducted to identify CTCF-binding proteins in AML cell lines. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to assess the impact of MAPK3 modulation on CTCF DNA binding, following treatment with an MAPK3 activator or inhibitor. Additionally, chromatin interactions were evaluated using 3C-qPCR, and specific enhancer sites at the SKAP2 locus were deleted using CRISPR-Cas9. Results demonstrated that IP-MS identified MAPK3 as a key CTCF-binding protein, indicating its potential role in AML chromatin regulation. MAPK3 significantly influences CTCF binding at distal intergenic regions upstream of SKAP2, as confirmed by ChIP-seq. Chromatin interaction analyses revealed that CTCF-regulated enhancer\u2013promoter interactions at SKAP2 are modulated by MAPK3 activity. Furthermore, deletion of enhancer regions E4 and E6 led to decreased SKAP2 expression. These findings highlight the critical role of MAPK3 in regulating CTCF-mediated chromatin interactions and suggest that targeting MAPK3-regulated chromatin remodeling could be a novel therapeutic strategy for AML.<\/jats:p>","DOI":"10.1093\/carcin\/bgaf073","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T12:32:22Z","timestamp":1761222742000},"source":"Crossref","is-referenced-by-count":1,"title":["MAPK3 modulates enhancer\u2013promoter interactions of SKAP2 in acute myeloid leukemia"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2260-3650","authenticated-orcid":false,"given":"Yanping","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital , Zhengzhou 450000 ,","place":["China"]},{"name":"Henan Key Laboratory of Molecular Pathology , Zhengzhou 450000 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