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10.1111/exd.12389

http://scihub22266oqcxt.onion/10.1111/exd.12389
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suck abstract from ncbi


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pmid25234828
      Exp+Dermatol 2014 ; 23 Suppl 1 (0 1 ): 2-6
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  • Ultraviolet irradiation represses TGF-? type II receptor transcription through a 38-bp sequence in the proximal promoter in human skin fibroblasts #MMPMID25234828
  • He T ; Quan T ; Fisher GJ
  • Exp Dermatol 2014[Oct]; 23 Suppl 1 (0 1 ): 2-6 PMID25234828 show ga
  • Transforming growth factor-? (TGF-?) is a major regulator of collagen gene expression in human skin fibroblasts. Cellular responses to TGF-? are mediated primarily through its cell surface type I (T?RI) and type II (T?RII) receptors. Ultraviolet (UV) irradiation impairs TGF-? signalling largely due to reduced T?RII gene expression, thereby decreasing type I procollagen synthesis, in human skin fibroblasts. UV irradiation does not alter either T?RII mRNA or protein stability, indicating that UV reduction in T?RII expression likely results from transcriptional or translational repression. To understand how UV irradiation regulates T?RII transcription, we used a series of T?RII promoter-luciferase 5'-deletion constructs (covering 2 kb of the T?RII proximal promoter) to determine transcriptional rate in response to UV irradiation. We identified a 137-bp region upstream of the transcriptional start site that exhibited high promoter activity and was repressed 60% by UV irradiation, whereas all other T?RII promoter reporter constructs exhibited either low promoter activities or no regulation by UV irradiation. Mutation of potential transcription factor binding sites within the promoter region revealed that an inverted CCAAT box (-81 bp from transcription start site) is required for promoter activity. Mutation of the CCAAT box completely abolished UV irradiation regulation of the T?RII promoter. Protein-binding assay, as determined by electrophoretic mobility-shift assays (EMSAs) using the inverted CCAAT box as probe (-100/-62), demonstrated significantly enhanced protein binding in response to UV irradiation. Super shift experiments indicated that nuclear factor Y (NFY) is able to binding to this sequence, but NFY binding was not altered in response to UV irradiation, indicating additional protein(s) are capable of binding this sequence in response to UV irradiation. Taken together, these data indicate that UV irradiation reduces T?RII expression, at least partially, through transcriptional repression. This repression is mediated by a 38-bp sequence in T?RII promoter, in human skin fibroblasts.
  • |Base Sequence [MESH]
  • |Binding Sites/genetics [MESH]
  • |CCAAT-Binding Factor/antagonists & inhibitors/genetics/metabolism [MESH]
  • |Cells, Cultured [MESH]
  • |Down-Regulation/radiation effects [MESH]
  • |Fibroblasts/metabolism/radiation effects [MESH]
  • |Humans [MESH]
  • |Models, Genetic [MESH]
  • |Mutagenesis, Site-Directed [MESH]
  • |Promoter Regions, Genetic/radiation effects [MESH]
  • |Protein Binding/radiation effects [MESH]
  • |Protein Serine-Threonine Kinases/*genetics [MESH]
  • |RNA, Small Interfering/genetics [MESH]
  • |Receptor, Transforming Growth Factor-beta Type II [MESH]
  • |Receptors, Transforming Growth Factor beta/*genetics [MESH]
  • |Skin/*metabolism/*radiation effects [MESH]


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