The epidermal differentiation complex (EDC) is a
gene complex comprising over fifty genes encoding proteins involved in the terminal
differentiation and
cornification of
keratinocytes, the primary cell type of the
epidermis. In humans, the complex is located on a 1.9
Mbp stretch within
chromosome 1q21.[1][2] The proteins encoded by EDC genes are closely related in terms of function, and evolutionarily they belong to three distinct
gene families: the cornified envelope precursor family, the
S100 protein family and the S100 fused type protein (SFTP) family.[3]
It has been hypothesized that the clustering of EDC genes occurred due to
duplication events which were evolutionarily favored during the adaptation to terrestrial environments.[3][4] In
sirenians, the main subtypes of EDC genes have been
conserved or even duplicated, such as the duplicated late cornified envelope genes of dugongs. On the other hand,
FLG genes of the SFTP family have become inactivated in sirenians, with the exception of
manatees.
Cetaceans have also lost function of FLG genes.[5] EDC proteins have been involved in a variety of skin disorders including
ichthyosis vulgaris,
atopic dermatitis and
psoriasis.[6]
History
The epidermal differentiation complex was first described in 1993,[1] and further characterized in 1996, when Dietmar Mischke and colleagues noted the "close functional cooperation among [eleven] structurally and evolutionary related genes".[2] By 2001, 37 genes had been identified as members of the EDC.[7] The number rose to 43 in 2002,[8] and by 2012 a total of 57 genes were considered part of the complex.[3]
EDC genes
Cornified envelope precursor family
As its name implies, the cornified envelope (CE) precursor family includes genes that encode the proteins forming the CE. The CE is a cross-linked matrix that surrounds terminally differentiated squamous keratinocytes after a process known as
cornification. CE precursor proteins are cross-linked by
transglutaminases.[3] The ratio of CE precursor proteins varies from tissue to tissue.[3] In the epidermis, the most abundant CE component is
loricrin (65-70%), while
involucrin is a minor component (<5%). The other CE proteins are classified as small proline-rich (SPRR) proteins, a subset of which is the late cornified envelope (LCE) protein group.[3]
The
S100 family comprises 17 genes and 6 pseudogenes. S100 proteins contain two
EF-hand motifs separated by a hinge region.[3] S100 proteins have various functions and are generally associated with abnormal epidermal differentiation.[3]S100A8 and
S100A9 (calgranulin A and B, respectively), dimerize to form
calprotectin. Calprotectin, psoriasin (
S100A7) and koebnerisin (
S100A7A) are
antimicrobial peptides.[3]
The S100 fused type protein (SFTP) family or fused gene family encompasses genes which are mainly expressed in
stratified epithelia and play a role in epithelial homeostasis.[3][9] Like S100 proteins, SFTPs contain two calcium-binding EF-hand motifs.[3] These proteins are associated with cytoplasmic
intermediate filaments as well as minor components of the CE.[3] Due to their homologous structure they are also known as filaggrin-like proteins.[10][11]
^
abVolz, Armin; Korge, Bernhard P.; Compton, John G.; Ziegler, Andreas; Steinert, Peter M.; Mischke, Dietmar (October 1993). "Physical Mapping of a Functional Cluster of Epidermal Differentiation Genes on Chromosome 1q21". Genomics. 18 (1): 92–99.
doi:
10.1006/geno.1993.1430.
PMID8276421.
^Hoffjan, S; Stemmler, S (September 2007). "On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis". British Journal of Dermatology. 157 (3): 441–449.
doi:
10.1111/j.1365-2133.2007.07999.x.
PMID17573887.
S2CID9434345.