Setdb1 Maintains Homeostasis Of Intestinal Stem Cells

Inflammatory bowel disease(IBD)is a complicated disease which has attracted decades of attentions with no clear etiology.Heredity has failed to explain its origin and is estimated to have only accounted for around 10%of IBD’s onset.Recently,more and more studies provide evidences that epigenetic modifications might contribute more to the onset of inflammatory bowel disease.We found a gene named Setdb1 mediating H3K9 tri-methylation decreased in published dataset of inflammatory bowel disease and hypothesized it might have some correlation with IBD’s onset.We then proved a pathway in the intestinal stem cells that used to maintain genome stability might correlate with the onset of human inflammatory bowel disease.Thus,providing new strategies to guide the medications of IBD.In detail,Setdb1 was used to silence endogenous retrovirus elements which comprise almost 8%percent of human genomes to maintain its stability.Once uncontrolled,those viruses like elements can be like real virus infection in the cell,which could hijack a cell’s regular progresses and lead to severe chaos.Once a cell senses the danger,it could choose to commit suicide in order to eliminate the virus.We articulated how those uncontrolled viruses like elements lead to the death of ISC(intestinal stem cell).While the normal nuclei acids of cells are A or B conformation,there is a Z nuclear acids binding protein(ZBP1)that can recognize those endogenous retrovirus elements(ERV).Once activated by ERV,ZBP1 then can recruit RIPK3 to form necrosome,RPK3 then can recruit and activate MLKL to carry out pore punching in the cell membrane and release cellular contents to the outer tissues.As a consequence,more lymphocytes would be recruited and aggravate the damaged barrier of intestine.