title: p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis.
abstract: During development, multipotent progenitor cells establish tissue-specific programs of gene expression. In this paper, we show that p63 transcription factor, a master regulator of epidermal morphogenesis, executes its function in part by directly regulating expression of the genome organizer Satb1 in progenitor cells. p63 binds to a proximal regulatory region of the Satb1 gene, and p63 ablation results in marked reduction in the Satb1 expression levels in the epidermis. Satb1(-/-) mice show impaired epidermal morphology. In Satb1-null epidermis, chromatin architecture of the epidermal differentiation complex locus containing genes associated with epidermal differentiation is altered primarily at its central domain, where Satb1 binding was confirmed by chromatin immunoprecipitation-on-chip analysis. Furthermore, genes within this domain fail to be properly activated upon terminal differentiation. Satb1 expression in p63(+/-) skin explants treated with p63 small interfering ribonucleic acid partially restored the epidermal phenotype of p63-deficient mice. These data provide a novel mechanism by which Satb1, a direct downstream target of p63, contributes in epidermal morphogenesis via establishing tissue-specific chromatin organization and gene expression in epidermal progenitor cells.
authors.affiliation: Centre for Skin Sciences, University of Bradford, Bradford BD7 1DP, England, UK.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Fessing
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Mardaryev
authors.forename: Michal R
authors.initials: MR
authors.lastname: Gdula
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Sharov
authors.forename: Tatyana Y
authors.initials: TY
authors.lastname: Sharova
authors.forename: Valentina
authors.initials: V
authors.lastname: Rapisarda
authors.forename: Konstantin B
authors.initials: KB
authors.lastname: Gordon
authors.forename: Anna D
authors.initials: AD
authors.lastname: Smorodchenko
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Poterlowicz
authors.forename: Giustina
authors.initials: G
authors.lastname: Ferone
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kohwi
authors.forename: Caterina
authors.initials: C
authors.lastname: Missero
authors.forename: Terumi
authors.initials: T
authors.lastname: Kohwi-Shigematsu
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Botchkarev
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D017404:In Situ Hybridization, Fluorescence; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D036961:Matrix Attachment Region Binding Proteins; D010750:Phosphoproteins; C469541:Satb1 protein, mouse; D015534:Trans-Activators; C486419:Trp63 protein, mouse