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

Abstract

Multiple 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.

Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors

“…In agreement with these findings, we report on the high expression of SYK in advanced Rb tumors compared to non-advanced Rb. In addition, we also discovered the differential expression of PRDM1 and TK1 in Rb subtypes, which are known epigenetic regulators in other cancers [60,61]. Our study also highlights the low expression of known canonical epigenetic readers such as BRD4, DNMT3A, and MGMT in advanced Rb tumors, highlighting a diverse epigenetic landscape in advanced tumors, extending our insights into Rb pathogenesis.…”

Identification of metabolic dysregulation and transcriptional networks in retinoblastoma reveals novel therapeutic targets

“…In agreement with these findings, we report high amplification of SYK in advanced Rb tumors compared to non-advanced Rb. In addition to it, we also report the differential expression of PRDM1 and TK1 in Rb subtypes, that are known epigenetic regulators in other cancers 58,59 . Our study also highlights the low expression of known canonical epigenetic readers like BRD4, DNMT3A and MGMT in advanced Rb tumors, highlighting a diverse epigenetic landscape in advanced tumors.…”