Epigenetic Enzyme Found Lacking in Some Patients with Crohn’s Disease; Mass General Study Reveals Essential Role of SP140 Protein in Innate Immune Function and Intestinal Health

A Massachusetts General Hospital (MGH) research team has found how a variant in an important epigenetic enzyme -- previously associated by population-based genetic studies with Crohn's disease and other immune disorders -- interferes with the action of the innate immune system, potentially upsetting the healthy balance between the microbial population of the gastrointestinal tract and the immune response. In a paper published in Science Immunology, the researchers report findings that SP140 -- an epigenetic reader protein that plays a critical role in determining whether or not target genes are expressed -- is essential to suppressing inappropriate gene expression in macrophages, innate immune cells that are critical to maintaining intestinal balance. "More than 400 enzymes write, read, or erase the epigenome, and mutations in these enzymes are some of the most prevalent perturbations in cancers, prompting rigorous efforts to identify compounds that could inhibit their function and reset gene expression," says Kate Jeffrey, Ph.D., of the MGH Gastrointestinal Unit and the Center for the Study of Inflammatory Bowel Disease, corresponding author of the article published in the March 3, 2017 issue of Science Immunology. The article is titled “Maintenance of Macrophage Transcriptional Programs and Intestinal Homeostasis by Epigenetic Reader SP140.” "Our knowledge of epigenomic enzyme mutations in immune-mediated disease is lagging well behind the cancer field, and our study -- the first to examine the function of SP140 in any detail -- shows how its loss in Crohn's disease triggers intestinal inflammation." SP140 is predominantly expressed in immune cells, and a variant form of the gene has been associated with Crohn's disease, multiple sclerosis, and chronic lymphocytic leukemia.
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