In a paper published online in advance in Nature this week, London Research Institute's Axel Behrens and his colleagues show that "unphosphorylated ... c-Jun interacts with Mbd3 and thereby recruits the nucleosome remodeling and histone deacetylation repressor complex." In colon cancer cells, depletion of Mbd3 increases histone acetylation at AP-1-dependent promoters, the authors observed, "which resulted in increased target gene expression." In mice, the gut-specific deletion of mbd3 "stimulated c-Jun activity and increase[s] progenitor cell proliferation," Behrens et al. show, adding that JNK-mediated c-Jun N-terminal phosphorylation relieves the repression of AP-1 target genes.
In this week's issue, Thomas Carell at Germany's Ludwig-Maximilians University discusses molecular computing, and says that the "DNA-based logic gates" idea, proposed by researchers at the Korea Advanced Institute of Science and Technology in an Angewandte Chemie paper , "could be a first step" for the field. In DNA logic-gates, Carell says, "specially designed DNA primers generate a sequence mismatch ... when they bind to an otherwise complementary DNA template" so that they prevent replication by a polymerase. He adds, though, that this can be "overcome in the presence of appropriate metal ions."
Over in Nature Cell Biology, an international research team reports that "TSPYL5 suppresses p53 levels and function by physical interaction with USP7." TSPYL5, a gene of unknown function located on chromosome 8q22 that is frequently amplified in breast cancer, "reduces p53 protein levels and inhibits activation of p53-target genes," the authors write. TSPYL5 expression "overrides p53-dependent proliferation arrest and oncogene-induced senescence," the team writes, adding that in cell-based assays, it found that TSPYL5 expression "contributes to oncogenic transformation."
In the latest installment of a series of articles in Nature Reviews Genetics on applications of next-generation sequencing, Harvard Medical School's Bradley Bernstein and his colleagues review recent papers that investigate histone modifications and "highlight the interplay between chromatin and genome function, dynamic variations in chromatin structure across cellular conditions, and emerging roles for large-scale domains and higher-ordered chromatin organization." Due to a "succession of technological advances over the past decade," Bernstein et al. write, researchers have made strides in charting histone modifications — and identifying their functional consequences — with improved accuracy.