InterPro domain: IPR023780

The CHROMO (CHRromatin Organization MOdifier) domain [ 1 , 2 , 3 , 4 ] is a conserved region of around 60 amino acids, originally identified in Drosophila modifiers of variegation. These are proteins that alter the structure of chromatin to the condensed morphology of heterochromatin, a cytologically visible condition where gene expression is repressed. In one of these proteins, Polycomb, the chromo domain has been shown to be important for chromatin targeting.

Proteins that contain a chromo domain appear to fall into 3 classes. The first class includes proteins having an N-terminal chromo domain followed by a region termed the chromo shadow domain, with weak but significant sequence similarity to the N-terminal chromo domain,[ 5 ], eg. Drosophila and human heterochromatin protein Su(var)205 (HP1). The second class includes proteins with a single chromo domain, eg. Drosophila protein Polycomb (Pc); mammalian modifier 3; human Mi-2 autoantigen and several yeast and Caenorhabditis elegans hypothetical proteins. In the third class paired tandem chromo domains are found, eg. in mammalian DNA-binding/helicase proteins CHD-1 to CHD-4 and yeast protein CHD1.

Functional dissections of chromo domain proteins suggests a mechanistic role for chromo domains in targeting chromo domain proteins to specific regions of the nucleus. The mechanism of targeting may involve protein-protein and/or protein/nucleic acid interactions. Hence, several line of evidence show that the HP1 chromo domain is a methyl-specific histone binding module, whereas the chromo domain of two protein components of the drosophila dosage compensation complex, MSL3 and MOF, contain chromo domains that bind to RNA in vitro [ 5 ].

The high resolution structures of HP1-family protein chromo and chromo shadow domain reveal a conserved chromo domain fold motif consisting of three beta strands packed against an alpha helix. The chromo domain fold belongs to the OB (oligonucleotide/oligosaccharide binding)-fold class found in a variety of prokaryotic and eukaryotic nucleic acid binding protein [ 6 ].

1. Imprinting a determined state into the chromatin of Drosophila. Trends Genet. 6, 416-21
2. A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants. Nucleic Acids Res. 19, 789-94
3. The chromo shadow domain, a second chromo domain in heterochromatin-binding protein 1, HP1. Nucleic Acids Res. 23, 3168-73
4. The chromo superfamily: new members, duplication of the chromo domain and possible role in delivering transcription regulators to chromatin. Nucleic Acids Res. 23, 4229-33
5. Molecular biology of the chromo domain: an ancient chromatin module comes of age. Gene 275, 19-29