title: The Epc-N domain: a predicted protein-protein interaction domain found in select chromatin associated proteins.
abstract: BACKGROUND
  An underlying tenet of the epigenetic code hypothesis is the existence of protein domains that can recognize various chromatin structures. To date, two major candidates have emerged: (i) the bromodomain, which can recognize certain acetylation marks and (ii) the chromodomain, which can recognize certain methylation marks.
  
  
  RESULTS
  The Epc-N (Enhancer of Polycomb-N-terminus) domain is formally defined herein. This domain is conserved across eukaryotes and is predicted to form a right-handed orthogonal four-helix bundle with extended strands at both termini. The types of amino acid residues that define the Epc-N domain suggest a role in mediating protein-protein interactions, possibly specifically in the context of chromatin binding, and the types of proteins in which it is found (known components of histone acetyltransferase complexes) strongly suggest a role in epigenetic structure formation and/or recognition. There appear to be two major Epc-N protein families that can be divided into four unique protein subfamilies. Two of these subfamilies (I and II) may be related to one another in that subfamily I can be viewed as a plant-specific expansion of subfamily II. The other two subfamilies (III and IV) appear to be related to one another by duplication events in a primordial fungal-metazoan-mycetozoan ancestor. Subfamilies III and IV are further defined by the presence of an evolutionarily conserved five-center-zinc-binding motif in the loop connecting the second and third helices of the four-helix bundle. This motif appears to consist of a PHD followed by a mononuclear Zn knuckle, followed by a PHD-like derivative, and will thus be referred to as the PZPM. All non-Epc-N proteins studied thus far that contain the PZPM have been implicated in histone methylation and/or gene silencing. In addition, an unusual phyletic distribution of Epc-N-containing proteins is observed.
  
  
  CONCLUSIONS
  The data suggest that the Epc-N domain is a protein-protein interaction module found in chromatin associated proteins. It is possible that the Epc-N domain serves as a direct link between histone acetylation and methylation statuses. The unusual phyletic distribution of Epc-N-containing proteins may provide a conduit for future insight into how different organisms form, perceive and respond to epigenetic information.
authors.affiliation: Division of Biological Sciences, University of California at San Diego, La Jolla, USA. jmperry@biomail.ucsd.edu
authors.forename: Jason
authors.initials: J
authors.lastname: Perry
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000201:enzymology / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000145:classification / Q000502:physiology; D051548:Histone Acetyltransferases / Q000737:chemistry*; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015032:Zinc / Q000378:metabolism
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D015032:Zinc