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Cellular responses to <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2 are mediated primarily through its cell surface type I (T\u03b2RI) and type II (T\u03b2RII) receptors. Ultraviolet (<jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content>) irradiation impairs <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2 signalling largely due to reduced T\u03b2RII gene expression, thereby decreasing type I procollagen synthesis, in human skin fibroblasts. UV irradiation does not alter either T\u03b2RII m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> or protein stability, indicating that <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> reduction in T\u03b2RII expression likely results from transcriptional or translational repression. To understand how <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation regulates T\u03b2RII transcription, we used a series of T\u03b2RII promoter\u2010luciferase 5\u2032\u2010deletion constructs (covering 2\u00a0kb of the T\u03b2RII proximal promoter) to determine transcriptional rate in response to <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation. We identified a 137\u2010bp region upstream of the transcriptional start site that exhibited high promoter activity and was repressed 60% by <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation, whereas all other T\u03b2RII promoter reporter constructs exhibited either low promoter activities or no regulation by <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation. Mutation of potential transcription factor binding sites within the promoter region revealed that an inverted <jats:styled-content style=\"fixed-case\">CCAAT<\/jats:styled-content> box (\u221281\u00a0bp from transcription start site) is required for promoter activity. Mutation of the <jats:styled-content style=\"fixed-case\">CCAAT<\/jats:styled-content> box completely abolished <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation regulation of the T\u03b2RII promoter. Protein\u2010binding assay, as determined by electrophoretic mobility\u2010shift assays (EMSAs) using the inverted <jats:styled-content style=\"fixed-case\">CCAAT<\/jats:styled-content> box as probe (\u2212100\/\u221262), demonstrated significantly enhanced protein binding in response to <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation. Super shift experiments indicated that nuclear factor Y (<jats:styled-content style=\"fixed-case\">NFY<\/jats:styled-content>) is able to binding to this sequence, but <jats:styled-content style=\"fixed-case\">NFY<\/jats:styled-content> binding was not altered in response to <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation, indicating additional protein(s) are capable of binding this sequence in response to <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation. Taken together, these data indicate that <jats:styled-content style=\"fixed-case\">UV<\/jats:styled-content> irradiation reduces T\u03b2RII expression, at least partially, through transcriptional repression. This repression is mediated by a 38\u2010bp sequence in T\u03b2RII promoter, in human skin fibroblasts.<\/jats:p>","DOI":"10.1111\/exd.12389","type":"journal-article","created":{"date-parts":[[2014,9,19]],"date-time":"2014-09-19T06:43:00Z","timestamp":1411108980000},"page":"2-6","source":"Crossref","is-referenced-by-count":7,"title":["Ultraviolet irradiation represses <scp>TGF<\/scp>\u2010\u03b2 type II receptor transcription through a 38\u2010bp sequence in the proximal promoter in human skin fibroblasts"],"prefix":"10.1111","volume":"23","author":[{"given":"Tianyuan","family":"He","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taihao","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Michigan Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary 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