Epidermal differentiation complex

The "epidermal differentiation complex", also known as EDC for short, is a gene family that is grouped together on chromosome 1 in the 1q21 region. The genes and gene families located there are called EDC genes and are present as clusters (see LCE3A-B-C below). This arrangement is also referred to as a gene complex. In the epidermal differentiation complex, more than fifty genes are now known that code for proteins involved in the terminal differentiation and keratinization of keratinocytes. The proteins encoded by the EDC genes are closely related in their function and, in evolutionary terms, belong to three different gene families:

• the "cornified envelope precursor family"
• the S100 protein family
• the family of S100 fusion proteins (SFTP).

It has been hypothesized that the accumulation of EDC genes is due to duplication events that were evolutionarily favored during adaptation to the terrestrial environment. EDC proteins are involved in a number of skin diseases, including ichthyosis vulgaris, atopic dermatitis and psoriasis.

Familie der Cornified-Envelope-Vorläufer: Die Familie der Cornified-Envelope-Vorläufer umfasst Gene, die für die Proteine ​​kodieren, die die sogenannte Cornified-Envelope bilden. Die Cornified-Envelope (CE) ist eine vernetzte Matrix, die terminal differenzierte Plattenepithelzellen nach dem Keratinisierungsprozess umgibt. Die CE-Vorläuferproteine ​​werden durch Transglutaminasen vernetzt. Das Verhältnis der CE-Vorläuferproteine ​​variiert von Gewebe zu Gewebe (Kypriotou M et al. 2012). In der Epidermis ist Loricrin (65-70%) die häufigste CE-Komponente, während Involucrin eine untergeordnete Komponente (<5%) darstellt. Die anderen CE-Proteine ​​werden als kleine prolinreiche (SPRR) Proteine ​​klassifiziert , von denen eine Untergruppe die Proteingruppe der späten Cornification-Envelope (LCE) ist (Kypriotou M et al. 2012). Die folgenden Proteinfamilien sind an der EDC beteiligt:

• Familie der Vorläufer der verhornten Hülle: Involucrin (IVL); Loricrin (LOR); Kleine prolinreiche Proteine ​​(SPRR-Proteine); SPRR1A (Cornifin A); SPRR1B (Cornifin B); SPRR2A; SPRR2B; SPRR2C; SPRR2D; SPRR2E; SPRR2F; SPRR2G; SPRR3; SPRR4
• Späte verhornte Hüllproteine ​​(LCE-Proteine): LCE1A; LCE1B; LCE1C; LCE1D; LCE1E; LCE1F; LCE2A; LCE2B; LCE2C; LCE2D; LCE3A; LCE3B; LCE3C; LCE3D; LCE3E; LCE41A; LCE5A; LCE6A; C1orf68
• S100-Proteine: Die S100-Familie besteht aus 17 Genen und 6 Pseudogenen. S100-Proteine ​​enthalten zwei EF-Hand-Motive, die durch eine Scharnierregion getrennt sind. S100-Proteine ​​haben verschiedene Funktionen und werden im Allgemeinen mit einer abnormalen epidermalen Differenzierung in Verbindung gebracht. S100A8 und S100A9 (Calgranulin A bzw. B) dimerisieren und bilden Calprotectin. Calprotectin , Psoriasin (S100A7) und Coebnerisin (S100A7A) sind antimikrobielle Peptide. Weitere S100-Proteine ​​sind: S100A7L2; S100A8 (Calgranulin A); S100A9 (Calgranulin B); S100A10; S100A11; S100A12 (Calgranulin C); S100A13; S100A14; S100A16.
• SFTP-Familie (S100-Proteine ​​vom Fusionstyp): Die Familie der S100-Fusionstyp-Proteine ​​(SFTP) umfasst Gene, die vorwiegend in geschichteten Epithelien exprimiert werden und eine Rolle bei der epithelialen Homöostase spielen. Wie die S100-Proteine ​​enthalten auch die SFTPs zwei Calcium-bindende EF-Hand-Motive. Aufgrund ihrer homologen Struktur werden sie auch als Filaggrin-ähnliche Proteine ​​bezeichnet: Filaggrin (FLG-Gen); Filaggrin-2 (FLG2); Trichohyalin (TCHH-Gen); Trichohyalin-like 1 (TCHHL1); Cornulin (CRNN); Repetin (RPTN); Hornerin (HRNR).

The genes of this family fulfill different functions, but together they are involved in a superordinate task, namely the complex differentiation process of the epidermis. The EDC genes encode both interacting structural proteins (see also Cornified envelope) and regulatory proteins of the epidermis.

Such arrangements in the human genome are rather rare. A well-known example of such a gene complex is the complex for the major histocompatibility genes (MHC, major histocompatibility complex) in humans. This gene complex is localized on chromosome 6. More than 50 genes are bundled in the 6p21.3 region, which carry out the complex tasks of the MHCs (presentation of antigens on the cell surface, their processing and introduction into the cell, etc.).

Arrangements such as those for the EDC are rather rare in the human genome.

A well-known example of such a gene complex is the complex for the major histocompatibility genes (MHC, major histocompatibility complex) in humans. This gene complex is localized on chromosome 6. More than 50 genes are bundled in the 6p21.3 region, which carry out the complex tasks of the MHCs (presentation of antigens on the cell surface, their processing and introduction into the cell, etc.).

The activity of the transcription factor NFAT5 in keratinocytes is controlled by osmotic stress. After ablation of NFAT5, the secretion of several matrix proteinases, including metalloproteinase-3 (Mmp3) and kallikrein-related peptidase 7 (Klk7), is significantly increased. This increase was found together with an increase in numerous members of the "epidermal differentiation complex" (EDC) ( Muhammad K et al. 2021)

1. Hoffjan S et al. (2007). On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis. British Journal of Dermatology 157: 441-449Kypriotou M et al. (2012) The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the 'fused genes' family. Experimental Dermatology 21: 643-649.

2. Mischke D et al. (1996) Genes Encoding Structural Proteins of Epidermal Cornification and S100 Calcium-Binding Proteins Form a Gene Complex ("Epidermal Differentiation Complex") on Human Chromosome 1q21". Journal of Investigative Dermatology 106: 989-992.

3. Muhammad K et al. (2021) NFAT5 Controls the Integrity of Epidermis. Front Immunol 12:780727.

4. Volz A et al. (1993) Physical Mapping of a Functional Cluster of Epidermal Differentiation Genes on Chromosome 1q21. Genomics 18: 92-99.