TALE homeodomain proteins regulate site-specific terminal differentiation, LCE genes and epidermal barrier

The epidermal barrier varies over the body surface to accommodate regional environmental stresses. Regional skin barrier variation is produced by site-dependent epidermal differentiation from common keratinocyte precursors and often manifests as site-specific skin disease or irritation. There is str...

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Published inJournal of cell science Vol. 124; no. Pt 10; pp. 1681 - 1690
Main Authors Jackson, Ben, Brown, Stuart J, Avilion, Ariel A, O'Shaughnessy, Ryan F L, Sully, Katherine, Akinduro, Olufolake, Murphy, Mark, Cleary, Michael L, Byrne, Carolyn
Format Journal Article
LanguageEnglish
Published England Company of Biologists 15.05.2011
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Summary:The epidermal barrier varies over the body surface to accommodate regional environmental stresses. Regional skin barrier variation is produced by site-dependent epidermal differentiation from common keratinocyte precursors and often manifests as site-specific skin disease or irritation. There is strong evidence for body-site-dependent dermal programming of epidermal differentiation in which the epidermis responds by altering expression of key barrier proteins, but the underlying mechanisms have not been defined. The LCE multigene cluster encodes barrier proteins that are differentially expressed over the body surface, and perturbation of LCE cluster expression is linked to the common regional skin disease psoriasis. LCE subclusters comprise genes expressed variably in either external barrier-forming epithelia (e.g. skin) or in internal epithelia with less stringent barriers (e.g. tongue). We demonstrate here that a complex of TALE homeobox transcription factors PBX1, PBX2 and Pknox (homologues of Drosophila Extradenticle and Homothorax) preferentially regulate external rather than internal LCE gene expression, competitively binding with SP1 and SP3. Perturbation of TALE protein expression in stratified squamous epithelia in mice produces external but not internal barrier abnormalities. We conclude that epidermal barrier genes, such as the LCE multigene cluster, are regulated by TALE homeodomain transcription factors to produce regional epidermal barriers.
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Present address: EpiStem Ltd, 48 Grafton Street, Manchester M13 9XX, UK
Present address: Geron Corporation, Menlo Park, CA 94025, USA
These authors contributed equally to this work
Present address: Immunbiology and Dermatology, Institute of Child Health, UCL, London WC1N 1EH, UK **Present address: Actelion Pharmaceuticals Ltd, Gewerbestr. 16, CH-4123 Allschwil, Switzerland
ISSN:0021-9533
1477-9137
DOI:10.1242/jcs.077552