Polycomb group (PcG) and trithorax Group (trxG) proteins, most of which associate with chromatin, regulate gene expression by binding as large complexes to DNA elements, known as PcG/trxG response elements (PREs), to reorganize the surrounding chromatin. A few PREs have been identified in the fly and analyses of Hox genes have suggested that PREs exist in the mouse, but no functional vertebrate PREs have been identified. The vertebrate hindbrain is subdivided into 8 metameric subunits, known as rhombomeres. Rhombomeres represent true embryologic compartments, each with its own unique transcriptional profile. Classic experiments have shown that, once their definitive transcriptional profile has been established, cells from adjacent rhombomeres cannot intermingle but sort themselves according to their rhombomeric origin. We have used this unique property of the hindbrain combined with mouse and fly genetics to examine mechanisms that remodel neural gene expression and to identify and validate of a PRE that regulates hindbrain segmentation.