RRC ID 49229
Author Goyal S, Suzuki T, Li JR, Maeda S, Kishima M, Nishimura H, Shimizu Y, Suzuki H.
Title RUNX1 induces DNA replication independent active DNA demethylation at SPI1 regulatory regions.
Journal BMC Mol Biol
Abstract BACKGROUND:SPI1 is an essential transcription factor (TF) for the hematopoietic lineage, in which its expression is tightly controlled through a -17-kb upstream regulatory region and a promoter region. Both regulatory regions are demethylated during hematopoietic development, although how the change of DNA methylation status is performed is still unknown.
RESULTS:We found that the ectopic overexpression of RUNX1 (another key TF in hematopoiesis) in HEK-293T cells induces almost complete DNA demethylation at the -17-kb upstream regulatory region and partial but significant DNA demethylation at the proximal promoter region. This DNA demethylation occurred in mitomycin-C-treated nonproliferating cells at both regulatory regions, suggesting active DNA demethylation. Furthermore, ectopic RUNX1 expression induced significant endogenous SPI1 expression, although its expression level was much lower than that of natively SPI1-expressing monocyte cells.
CONCLUSIONS:These results suggest the novel role of RUNX1 as an inducer of DNA demethylation at the SPI1 regulatory regions, although the mechanism of RUNX1-induced DNA demethylation remains to be explored.
Volume 18(1)
Pages 9
Published 2017-4-4
DOI 10.1186/s12867-017-0087-y
PII 10.1186/s12867-017-0087-y
PMID 28376714
PMC PMC5381148
MeSH Base Sequence Cell Line Core Binding Factor Alpha 2 Subunit / genetics Core Binding Factor Alpha 2 Subunit / metabolism* DNA Methylation* DNA Replication* Gene Expression Regulation Humans Promoter Regions, Genetic Proto-Oncogene Proteins / genetics* Trans-Activators / genetics* Up-Regulation
IF 1.658
Times Cited 1
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393).
Human and Animal Cells 293T(RCB2202)