Chromatin boundaries and insulators are transcriptional regulatory elements that modulate interactions between enhancers and promoters and protect genes from silencing effects by the adjacent chromatin. Originally discovered in Drosophila, insulators have now been found in a variety of organisms, ranging from yeast to humans. They have been found interspersed with regulatory sequences in complex genes and at the boundaries between active and inactive chromatin. Insulators might modulate transcription by organizing the chromatin fiber within the nucleus through the establishment of higher-order domains of chromatin structure.