Late Cornified Envelope Family in Differentiating Epithelia—Response to Calcium and Ultraviolet Irradiation

Abstract

The late cornified envelope (LCE) gene cluster within the epidermal differentiation complex on human chromosome one (mouse chromosome three) contains multiple conserved genes encoding stratum-corneum proteins. Within the LCE cluster, genes form "groups" based on chromosomal position and protein homology. We link a recently accepted nomenclature for the LCE cluster (formerly XP5, small proline-rich-like, late-envelope protein genes) to gene structure, groupings, and chromosomal organization, and carry out a pan-cluster quantitative expression analysis in a variety of tissues and environmental conditions. This analysis shows that (i) the cluster organizes into two "skin" expressing groups and a third group with low-level, tissue-specific expression patterns in all barrier-forming epithelia tested, including internal epithelia; (ii) LCE genes respond "group-wise" to environmental stimuli such as calcium levels and ultraviolet (UV) light, highlighting the functional significance of groups; (iii) in response to UV stimulation there is massive upregulation of a single, normally quiescent, non-skin LCE gene; and (iv) heterogeneity occurs between individuals with one individual lacking expression of an LCE skin gene without overt skin disease, suggesting LCE genes affect subtle attributes of skin function. This quantitative and pan-cluster expression analysis suggests that LCE groups have distinct functions and that within groups regulatory diversification permits specific responsiveness to environmental challenge.

Gene expression changes in the host response between resistant and susceptible inbred mouse strains after influenza A infection

“…Expression of the Sprr and Lce genes is associated with epidermal terminal differentiation [38] and psoriasis [39]. Lce genes are organized in three sub-clusters which exhibit common regulation of gene expression [40]. In the mouse, genes from all groups are also expressed in stomach, umbilical cord and cornea (http://biogps.gnf.org/?referer¼symatlas#goto¼ welcome).…”

Psoriasis Risk Genes of the Late Cornified Envelope-3 Group Are Distinctly Expressed Compared with Genes of Other LCE Groups

“…8 This region is enriched for genes expressed during epidermal differentiation including loricrin, involucrin, filaggrin, the small proline-rich protein genes, and the LCE genes. 9,10 With 18 members, the LCE gene family is divided into six groups, LCE1 to LCE6, based on similarities of amino acid sequences, genomic organization, and patterns of expression. 9 The role of the LCE proteins in epidermal biology has not been extensively studied.…”

“…9,10 With 18 members, the LCE gene family is divided into six groups, LCE1 to LCE6, based on similarities of amino acid sequences, genomic organization, and patterns of expression. 9 The role of the LCE proteins in epidermal biology has not been extensively studied. In mice, it was observed that members of the Lce1 group are expressed rather late in epithelial development, where they are incorporated into the cornified envelope via cross-linking by transglutaminases.…”

“…Studies in cultured keratinocytes demonstrated that LCE2 expression is induced by Ca ϩϩ , whereas UVB irradiation induced expression of LCE3E and members of the LCE1 and LCE2 groups. 9 In a previous study based on the observed LCE3C induction in lesional psoriatic skin and injured skin, a role for the LCE3 genes in skin barrier repair was hypothesized. 4 The present study sought to extend these studies, to find a possible clue to the mechanistic relationship between the LCE3B/C deletion and psoriasis.…”

Mouse models: Psoriasis: an epidermal disease after all?

“…The genes encoding S100A8 and A9 are localized to the epidermal differentiation complex (EDC) on human chromosome 1q21.3, together with at least 58 genes involved in keratinocyte terminal differentiation. 12 Along with several other EDC genes, S100A8 and S100A9 are strongly overexpressed in psoriasis. 13 While both linkage and association to the EDC have been reported in psoriasis, 14 these results remain to be widely confirmed.…”