Friday Science Review: June 10, 2011
June 10, 2011
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Silence is Golden
University of British Columbia ♦ BC Cancer Agency ♦ Institute for Virus Research ♦ Kyoto University
Published in Cell Stem Cell, June 3, 2011
Researchers analyzing the genome wide repression of genes and other repetitive elements, like endogenous retroviruses (ERVs), have come upon some findings that illustrate how epigenetic silencing occurs in mouse embryonic stem cells (mESCs). Epigenetic silencing of genes typically serves to repress the expression of very specific portions of DNA, and it has also been known to repress snippits of viral DNA found in the long winding portions of DNA between genes. To analyze what would happen in the absence of epigenetic silencing, researchers genetically modified mESCs to be null for DNA methyltransferase and the H3K9 methyltransferase Setdb1 — two enzymes that are very active in gene silencing via the deposition of methyl groups to DNA (preventing transcription of genes). Interestingly, as opposed to observing an overlap in the genetic elements that were activated in the absence of these enzymes, researchers found that two very distinct sets of genes were activated. About 15% of the genes activated in the absence of Setdb1 were activated by the promoter of an endogenous retrovirus. In as much as half of these cases, viral transcripts were fused to regular gene transcripts producing chimeric transcripts. These findings provide a role for the methyltransferase Setdb1 in silencing retro-elements and repressing aberrant transcriptional events that could lead to potentially harmful proteins downstream.
Inflammation, Innate Immunity, and the Intestine
McGill University ♦ Published in Nature, June 2, 2011
A key mechanism by which the intestine protects itself from the threat of foreign-invaders, the likes of pathogens and other microbes, is through the nucleotide-binding and oligomerization domain (NOD) proteins located in the interior of intestinal cells. These pattern recognition receptors have been highly conserved throughout the evolution of the innate immune system due to their importance in sensing infection and other dangerous signals. NOD proteins have the ability to sense proteins on the extremity of microorganisms and in response elicit a signaling cascade leading to the release of chemical messengers known as cytokines that drive an immune response and inflammation. Until recently , the exact nature of the signaling mechanisms controlling this process were unknown but as a result of some work with RNAi on the genome scale we have a much better understanding. Researchers at McGill conducted a small interfering RNA screen of 7170 human “druggable” genes to identify candidate genes that modulate the NOD inflammatory response. In doing so they identified the protein BID as an activator of NOD signaling. Macrophages from mice lacking the BID gene are highly defective in cytokine production while the mice themselves are unresponsive to local or systemic exposure to molecules that activate NOD signaling. Interestingly BID has a key role in programmed cell death, strengthening the already existing theory that programmed cell death and immunity are linked on some level.