Biological complexity: epigenetic controls in intestine (Introduction)

by David Turell , Monday, March 06, 2017, 15:01 (2602 days ago) @ David Turell

New research shows how an "epigenetic reader" controls epigenetic marks:

http://www.the-scientist.com/?articles.view/articleNo/48729/title/Key-Regulator-of-Inte...

"Jeffrey and colleagues decided to focus on SP140 because prior genome-wide association studies characterized it as the culprit behind a number of autoimmune disorders, including Crohn’s disease. In the latest study, the researchers used ChiP-seq analysis to isolate the epigenetic reader and the DNA bound to it, and discovered that SP140 occupied transcriptional start sites in human macrophages. They also found that depleting SP140 in macrophages (from both healthy humans and mice) in cell culture severely impaired their abilities to be activated.

"In addition, the team knocked out the SP140 gene in the immune systems of model mice, finding that the loss of this epigenetic reader weakened the rodents’ intestinal barrier defenses, altered the balance of their gut microbes, and exacerbated intestinal inflammation.

“'It’s interesting that [SP140] both changes the response to pathogens and makes colitis worse,” said Alexander Marson, an assistant professor of microbiology and immunology at the University of California, San Francisco, who was not involved in the study. “Figuring out exactly what it does in the context of infection in vivo will be interesting.”

“'Initially, when we found this epigenetic mediator to be immune-restricted, we thought that would make a great therapeutic target because . . . you may not get off-target effects,” Jeffrey said. “But it turns out that you would not want to inhibit this particular epigenetic reader because its loss results in intestinal inflammation.'”

Comment: Obviously the living body must be able to add and subtract epigenetic marks as necessary, adapting and un-adapting. More complexity found.