Eukaryotic chromosomes are divided into independent domains with distinct chromatin structures (euchromatin and heterochromatin). Most genes reside within euchromatic domains that are associated with irregular nucleosomal arrays enriched in histones (basic proteins of cell nuclei) that are hyperacetylated and methylated at lysine 4 of histone H3. Such nucleosomal modifications establish chromatin structures that are generally permissive to transcription factor association and gene transcription.

Within a given euchromatic domain, neighboring genes often display different expression patterns, indicating that distinct functional domains exist within large euchromatic regions. Transcriptionally active euchromatic domains are interspersed with hetero-chromatic regions that are gene-poor and organized into regular arrays of hypoacetylated nucleosomes that are methylated at lysine 9 of histone H3. Heterochromatic histone modifications generate a platform for interaction with proteins that spread in cis direction along the chromosome and limit transcription factor access to target sequences. A class of deoxyribonucleic acid (DNA) elements known as insulators defines the junctions between structural and functional chromatin domains.