Impact of CYLD on chromatin structure and histone methylation in malignant melanoma

• DOI: 10.3892/ijmm.2022.5122
• Publication Date: 2022-03-15T11:59:01Z
• Authors: Mandy Schott; Melanie Kappelman...; Stefan Fischer; Maite Fernandez‑B...; Antonio Pineda‑Lu...; Matías Ávila; Silke Kuphal; Anja-Katrin Bosse...
• Keywords: Histone Methylation

The tumor suppressive role of CYLD lysine 63 deubiquitinase (CYLD) is known in melanoma. To the best our knowledge, however, precise mechanism underlying function has yet to be clarified. In present study, a novel melanoma mouse model was generated, which revealed accelerated growth Cyld‑knockout (Cyld‑/‑) compared with Cyld‑wild‑type (Cyld+/+) mice. determine molecular mechanism, mutation analysis primary tumor‑derived cell lines from Cyld+/+ and Cyld‑/‑ mice performed using RNA sequencing data. Variant calling no common mutations cells. Thus, epigenetic processes influencing development progression were investigated. Initial expression pattern hypermethylated genes (suppressor cytokine signalling, methylthioadenosine phosphorylase, cadherin 1) presence or absence 5'‑Aza‑deoxyctidine treatment that does not play key DNA methylation. Chromatin accessibility histone H3 modification assay uncovered formation chromatin structure. Subsequent inhibitor experiments confirmed effect on H3K9me2 level associated heterochromatin. Furthermore, enhanced H3K9 dimethylation cells upregulation euchromatic methyltransferase 2 (EHMT2). Moreover, specific EHMT2, CM272, resulted decreased proliferation relaxation compact Cyld‑deficient These results reveal methylation packaging.