E2F1 mediates the downregulation of POLD1 in replicative senescence.

In this study, four potential CpG islands in the POLD1 promoter were found, and the methylation levels of the POLD1 promoter were increased in aging 2BS cells, WI-38 cells and peripheral blood lymphocytes, especially at a single site, CpG 36, in CpG island 3. Then, the transcription factor E2F1 was observed to bind to these sites. The binding affinity of E2F1 for the POLD1 promoter was found to show age-related attenuation and was confirmed to be positively regulated by the E2F1 level and negatively regulated by POLD1 promoter methylation. Moreover, cell senescence characteristics were observed in the cells transfected with shRNA-E2F1 and could contribute to the downregulation of POLD1 induced by the E2F1 decline. Collectively, these results indicated that the attenuation of the binding affinity of E2F1 for the POLD1 promoter, mediated by an age-related decline in E2F1 and increased methylation of CpG island 3, downregulates POLD1 expression in aging. PMID: 30895337 [PubMed - as supplied by publisher]
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research