Differential epigenetic regulation between the alternative promoters, PRDM1? and PRDM1?, 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 PRDM1? isoform is an alternative promoter of the PRDM1 gene that may interfere with the normal role of the PRDM1? isoform. To explain the induction of the PRDM1? 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 PRDM1? and PRDM1? promoters, respectively, and prominent H3K4me1 and H3K9me2 enrichment at the PRDM1? promoter in non-expressing cell lines compared to PRDM1?-expressing cell lines. After treatment with drugs that inhibit DNA methylation, we were able to modify the activity of the PRDM1? promoter but not that of the PRDM1? promoter. Epigenetic drugs may offer the ability to control the expression of the PRDM1?/PRDM1? promoters as components of novel therapeutic approaches.

SUBMITTER: Romero-Garcia R 

PROVIDER: S-EPMC7522722 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature