Related Experiment Video
Updated: Jun 16, 2026

Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
A milieu of regulatory elements in the epidermal differentiation complex syntenic block: implications for atopic
Cristina de Guzman Strong1, Sean Conlan, Clayton B Deming
1Genetics and Molecular Biology Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
Abstract:
Two common inflammatory skin disorders with impaired barrier, atopic dermatitis (AD) and psoriasis, share distinct genetic linkage to the Epidermal Differentiation Complex (EDC) locus on 1q21. The EDC is comprised of tandemly arrayed gene families encoding proteins involved in skin cell differentiation. Discovery of semi-dominant mutations in filaggrin (FLG) associated with AD and a copy number variation within the LCE genes associated with psoriasis provide compelling evidence for the role of EDC genes in the pathogenesis of these diseases. To date, little is known about the potentially complex regulatory landscape within the EDC. Here, we report a computational approach to identify conserved non-coding elements (CNEs) in the EDC queried for regulatory function. Coordinate expression of EDC genes during mouse embryonic skin development and a striking degree of synteny and linearity in the EDC locus across a wide range of mammalian (placental and marsupial) genomes suggests an evolutionary conserved regulatory milieu in the EDC. CNEs identified by comparative genomics exhibit dynamic regulatory activity (enhancer or repressor) in differentiating or proliferating conditions. We further demonstrate epidermal-specific, developmental in vivo enhancer activities (DNaseI and transgenic mouse assays) in CNEs, including one within the psoriasis-associated deletion, LCE3C_LCE3B-del. Together, our multidisciplinary study features a network of regulatory elements coordinating developmental EDC gene expression as an unexplored resource for genetic variants in skin diseases.
Related Concept Videos
Renewal of Skin Epidermal Stem Cells
Master Transcription Regulators
Clinical Applications of Epidermal Stem Cells
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
The Skin Microbiota
Skin Diseases and Disorders
Gram-positive Staphylococcus spp. and Streptococcus spp. are responsible for many of the most common skin infections. However, many...