The Study Of Knock-out UHRF1 Leading To Cell Death In Somatic Cell

UHRF1 is a multi-domain and multi-functional protein which is required for cell cycle progression and maintaining DNA methylation.The mechanism is not clear for knockout UHRF1 in somatic cell to lead to cell death.Here,we use HC T116-flox-1 cell line which contains UHRF1 conditional allele and the forth exon flanked by loxp sites.Cre recombinase mediated disruption of conditional allele results knockout UHRF1.In our study,we show that loss of UHRF1 leads to reduce DNA methylation in genome,couple with S phase decrease and G2/M phase increase in cell cycle,besides,increase cell apoptosis,but we can not detect increasing for the focis of ?H2AX.Further study we find that UHRF1 knockout induce activating interferon signaling pathway and retrovirus elements transcription.Our results thus show that UHRF1 is essential for cell survival and proliferation,and loss of UHRF1 results cell cycle arrest and induce activating interferon signaling pathway and retrovirus elements transcription and leads cell apoptosis.