title: TALE homeodomain proteins regulate site-specific terminal differentiation, LCE genes and epidermal barrier.
abstract: 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.
authors.affiliation: Centre for Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Jackson
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Brown
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Avilion
authors.forename: Ryan F L
authors.initials: RF
authors.lastname: O'Shaughnessy
authors.forename: Katherine
authors.initials: K
authors.lastname: Sully
authors.forename: Olufolake
authors.initials: O
authors.lastname: Akinduro
authors.forename: Mark
authors.initials: M
authors.lastname: Murphy
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cleary
authors.forename: Carolyn
authors.initials: C
authors.lastname: Byrne
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012879:Skin Physiological Phenomena / Q000235:genetics*
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C490797:Tgif1 protein, mouse