RT Journal Article
T1 Differential epigenetic regulation between the alternative promoters, PRDM1α and PRDM1β, of the tumour suppressor gene PRDM1 in human multiple myeloma cells.
A1 Romero-Garcia, Raquel
A1 Gomez-Jaramillo, Laura
A1 Mateos, Rosa Maria
A1 Jimenez-Gomez, Gema
A1 Pedreño-Horrillo, Nuria
A1 Foncubierta, Esther
A1 Rodriguez-Gutierrez, Juan Francisco
A1 Garzon, Sebastian
A1 Mora-Lopez, Francisco
A1 Rodriguez, Carmen
A1 Valor, Luis M
A1 Campos-Caro, Antonio
K1 Área de Gestión Sanitaria de Jerez, Costa Noroeste y Sierra de Cádiz
K1 Apoptosis
K1 Cell Line, Tumor
K1 DNA Methylation
K1 Down-Regulation
K1 Epigenesis, Genetic
AB 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.
PB Nature Publishing Group
YR 2020
FD 2020-09-07
LK http://hdl.handle.net/10668/16333
UL http://hdl.handle.net/10668/16333
LA en
NO Romero-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):15899
NO Tis research was funded by Instituto de Salud Carlos III through Projects PI11/01091 and PI15/01147 to ACC (Co-funded by the European Regional Development Fund/European Social Fund "Investing in your future"),Consejería de Innovación, Ciencia y Empresa-Junta de Andalucía through Project P09-CTS-5445 to ACC, and Consejería de Salud-Junta de Andalucía with Projects PI-0265/2005 and PI-0817/2012 to ACC and FML, respectively. LMV is the recipient of a Miguel Servet I contract (CP15/00180) from Instituto de Salud Carlos III and Fondo Social Europeo 2014-2020.
DS RISalud
RD Apr 5, 2025