In a paper published online in advance in Nature this week, researchers at the M.D. Anderson Cancer Center and their international colleagues report that the chromatin regulator tripartite motif-containing 24 "functions in humans as a reader of dual histone marks by means of tandem plant homeodomain and bromodomain regions." Aberrant TRIM24 expression, the team shows, correlates negatively with survival in breast cancer patients. Based on their analyses, the researchers suggest that "the PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis."
In another Nature advance online publication, a team led by investigators at the Salk Institute suggests that CRTC3 may play a role in human obesity. In two distinct cohorts of Mexican-Americans, the team found a common CRTC3 variant with increased transcriptional activity that is associated with adiposity. "Crtc3 promotes obesity by attenuating β-adrenergic receptor signaling in adipose tissue," the authors write.
While working with three ascomycete yeasts — Saccharomyces cerevisiae, Kluyveromyces lactis, and Candida albicans — a trio of researchers at the University of California, San Francisco, detected what they've since determined to be a gene network re-wiring event, in which "a new level of transcriptional control" was incorporated into "an ancient circuit." While the three species all have three cell types, the UCSF researchers found that the Mata1–Matα2 heterodimer present in the ancestral mating circuit represses the same four genes in each through an intermediate regulatory protein, Rme1. Further, the authors add, "a new phenotype was produced by the rewiring: unlike S. cerevisiae and C. albicans, K. lactis integrates nutritional signals, by means of Rme1, into the decision of whether or not to mate."
Investigators at the Stanford University School of Medicine report chromatin signatures in human embryonic stem cells that "identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, monomethylation of histone H3 at lysine 4, and low nucleosomal density." Elements in one class are associated with H3K27 acetylation, show overlap with hESC enhances, and "are located proximally to genes expressed in hESCs and the epiblast." Those in the other do not show H3K27 acetylation, though they do show enriched H3K27 tri-methylation. These so-called "poised enhancers" of the second are linked to inactive genes and are "involved in orchestrating early steps in embryogenesis," the authors write. Taken together, the authors say that their data "demonstrate that early developmental enhancers are epigenetically pre-marked in hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory elements."