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Klf4 and corticosteroids activate an overlapping set of transcriptional targets to accelerate in utero epidermal barrier acquisition

Patel, Satyakam ; Xi, Zong Fang ; Seo, Eun Young ; McGaughey, David ; Segre, Julia A

Proceedings of the National Academy of Sciences - PNAS, 2006-12, Vol.103 (49), p.18668-18673 [Periódico revisado por pares]

United States: National Acad Sciences

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  • Título:
    Klf4 and corticosteroids activate an overlapping set of transcriptional targets to accelerate in utero epidermal barrier acquisition
  • Autor: Patel, Satyakam ; Xi, Zong Fang ; Seo, Eun Young ; McGaughey, David ; Segre, Julia A
  • Assuntos: Adrenal Cortex Hormones - physiology ; Animals ; Biological Sciences ; Cell Line, Tumor ; Dehydration ; Epidermis - embryology ; Female ; Gene Expression Regulation, Developmental - physiology ; Gene Targeting ; Genetics ; Infections ; Kruppel-Like Transcription Factors - physiology ; Male ; Mice ; Premature birth ; Skin ; Steroids ; Transcription, Genetic - physiology
  • É parte de: Proceedings of the National Academy of Sciences - PNAS, 2006-12, Vol.103 (49), p.18668-18673
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Author contributions: S.P., Z.F.X., E.Y.S., and J.A.S. designed research; S.P., Z.F.X., E.Y.S., D.M., and J.A.S. performed research; S.P., Z.F.X., E.Y.S., and J.A.S. analyzed data; and J.A.S. wrote the paper.
    Communicated by Eric S. Lander, The Broad Institute, Cambridge, MA, October 12, 2006
  • Descrição: Premature infants are at an increased risk for infections and dehydration because of incomplete development of the epidermis, which attains its essential function as a barrier only during the last stages of in utero development. When a premature birth is anticipated, antenatal corticosteroids are administered to accelerate lung epithelium differentiation. One pleiotropic, but beneficial, effect of antenatal corticosteroids is acceleration of skin barrier establishment by an unknown mechanism. In mice, the transcription factor Klf4 is both necessary and sufficient, within a developmental field of competence, to establish this skin barrier, as demonstrated by targeted ablation and transgenic expression of Klf4, respectively. Here, we report that Klf4 and corticosteroid treatment coordinately accelerate barrier acquisition in vivo . Transcriptional profiling reveals that the genes regulated by corticosteroids and Klf4 during the critical window of epidermal development significantly overlap. KLF4 activates the proximal promoters of a significant subset of these genes. Dissecting the intersection of the genetic and pharmacological pathways, regulated by KLF4 and corticosteroids, respectively, leads to a mechanistic understanding of the normal process of epidermal development in utero . development transcription factor skin glucocorticoid receptor
  • Editor: United States: National Acad Sciences
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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