Differential epigenetic regulation between the alternative promoters, PRDM1α and PRDM1β, of the tumour suppressor gene PRDM1 in human multiple myeloma cells.

Romero-Garcia, RaquelGomez-Jaramillo, LauraMateos, Rosa MariaJimenez-Gomez, GemaPedreño-Horrillo, NuriaFoncubierta, EstherRodriguez-Gutierrez, Juan FranciscoGarzon, SebastianMora-Lopez, FranciscoRodriguez, CarmenValor, Luis MCampos-Caro, Antonio2023-02-092023-02-092020-09-07Romero-García R, Gómez-Jaramillo L, Mateos RM, Jiménez-Gómez G, Pedreño-Horrillo N, Foncubierta E, et al. Differential epigenetic regulation between the alternative promoters, PRDM1α and PRDM1β, of the tumour suppressor gene PRDM1 in human multiple myeloma cells. Sci Rep. 2020 Sep 28;10(1):15899http://hdl.handle.net/10668/16333Multiple myeloma (MM) is a B-cell neoplasm that is characterized by the accumulation of malignant plasma cells in the bone marrow. The transcription factor PRDM1 is a master regulator of plasma cell development and is considered to be an oncosuppressor in several lymphoid neoplasms. The PRDM1β isoform is an alternative promoter of the PRDM1 gene that may interfere with the normal role of the PRDM1α isoform. To explain the induction of the PRDM1β isoform in MM and to offer potential therapeutic strategies to modulate its expression, we characterized the cis regulatory elements and epigenetic status of its promoter. We observed unexpected patterns of hypermethylation and hypomethylation at the PRDM1α and PRDM1β promoters, respectively, and prominent H3K4me1 and H3K9me2 enrichment at the PRDM1β promoter in non-expressing cell lines compared to PRDM1β-expressing cell lines. After treatment with drugs that inhibit DNA methylation, we were able to modify the activity of the PRDM1β promoter but not that of the PRDM1α promoter. Epigenetic drugs may offer the ability to control the expression of the PRDM1α/PRDM1β promoters as components of novel therapeutic approaches.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Área de Gestión Sanitaria de Jerez, Costa Noroeste y Sierra de CádizApoptosisCell Line, TumorDNA MethylationDown-RegulationEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansMultiple MyelomaPositive Regulatory Domain I-Binding Factor 1Promoter Regions, GeneticDifferential epigenetic regulation between the alternative promoters, PRDM1α and PRDM1β, of the tumour suppressor gene PRDM1 in human multiple myeloma cells.research article32985591open accessFactor 1 de unión al dominio 1 de regulación positivaMieloma múltipleRegiones promotoras genéticasRegulación neoplásica de la expresión génica10.1038/s41598-020-72946-z2045-2322PMC7522722https://www.nature.com/articles/s41598-020-72946-z.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522722/pdf