In the cell’s nucleus, neighborhoods matter. According to a new study from Howard Hughes Medical Institute (HHMI) researchers corralling certain genes at the edge of the nucleus, developing immune cells can control a gene’s activity and keep it switched off.  The finding comes as the result of researchers’ efforts to understand how blood stem cells mature into the various types of immune system cells that recognize invading bacteria and viruses.   Both B cells and T cells- immune cells of our body- mature from blood stem cells, and use the same set of proteins to organize activation of their receptor genes. But the set of genes that encodes B cell antibodies is different from the set of genes that encodes T cell receptors.  So given their developmental similarities, how do B and T cells avoid turning on the wrong genes?  In blood stem cells, the gene segments that encode both antibodies and T cell receptors are attached to the inside of the nuclear membrane.  The group had found that the antibody genes were being moved [toward the center of] the nucleus in B cells as they developed. In developing T cells, on the other hand, those same gene segments—which are never switched on—remained stuck to the membrane.   This organization probably creates areas whose genetic occupants could not be activated so that developing T cells might leave the unneeded antibody genes pinned against the nuclear membrane to avoid the potential for mistakes.  The team attached a binding site for the protein LacI to a gene that makes a cell resistant to the cell-killing drug hygromycin, and inserted the assembly into a mouse cell. The researchers chose the hygromycin resistance gene because it provided any easy way to test gene activity; when exposed to the drug, only cells with an active gene would survive.  In the same cells, they also activated LacI, which dutifully latched on. But in a bit of scientific trickery, the researchers first fused LacI to two other proteins. The first was green fluorescent protein which glows brightly and allowed the team to identify the assembly’s location. The second was a protein called emerin, which normally resides in the nuclear membrane. The results showed that regardless of the other proteins and DNA that the researchers had attached to it, the cell recognized that emerin belonged in the membrane, and dragged it there.  This shows that repositioning of genes and hence changing the neighborhood has consequences.