chromodomains

Chromodomains are small, evolutionarily conserved protein domains, typically 40 to 60 amino acids in length, found in a variety of chromatin-associated proteins. They function as readers of histone modifications and help direct effector activities to particular chromatin regions.

Most chromodomains recognize methylated lysine residues on histone tails, particularly trimethyllysines. The best characterized examples are HP1 proteins that bind H3K9me3 to promote heterochromatin formation, and Polycomb group CBX proteins that recognize H3K27me3 to support gene silencing. Some chromodomains in chromatin remodelers or transcriptional regulators, such as CHD1, bind H3K4me3 and associate with transcriptionally active regions. Specificity among chromodomains can vary with the surrounding histone sequence and with interactions to other proteins.

Structurally, the canonical chromodomain folds into a compact module consisting of a three-stranded beta sheet packed against an alpha helix. A conserved set of aromatic residues forms an aromatic cage that encapsulates the methylated lysine, enabling recognition through cation-π interactions. Variants of the motif may alter the binding mode or target nonhistone ligands in some contexts.

Biologically, chromodomains act as readers that recruit chromatin-modifying enzymes, remodelers, or transcriptional regulators to defined chromatin states, thereby contributing to processes such as heterochromatin formation, gene silencing, and regulation of gene expression. Dysregulation of chromodomain-containing proteins has been linked to developmental abnormalities and cancer.