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Title

Glucocorticoid receptor and Klf4 co-regulate anti-inflammatory genes in keratinocytes.

AuthorsSevilla, Lisa M. ; Latorre, Víctor; Carceller, Elena; Boix, Julia; Vodák, Daniel; Mills, Ian Geoffrey; Pérez, Paloma
KeywordsGlucocorticoid receptor
Inflammation
Keratinocyte
Kruppel-like factor 4
Transcription
Issue Date19-May-2015
PublisherElsevier
CitationMolecular and Cellular Endocrinology 412:281-289 (2015)
AbstractThe glucocorticoid (GC) receptor (GR) and Kruppel-like factor Klf4 are transcription factors that play major roles in skin homeostasis. However, whether these transcription factors cooperate in binding genomic regulatory regions in epidermal keratinocytes was not known. Here, we show that in dexamethasone-treated keratinocytes GR and Klf4 are recruited to genomic regions containing adjacent GR and KLF binding motifs to control transcription of the anti-inflammatory genes Tsc22d3 and Zfp36. GR- and Klf4 loss of function experiments showed total GR but partial Klf4 requirement for full gene induction in response to dexamethasone. In wild type keratinocytes induced to differentiate, GR and Klf4 protein expression increased concomitant with Tsc22d3 and Zfp36 up-regulation. In contrast, GR-deficient cells failed to differentiate or fully induce Klf4, Tsc22d3 and Zfp36 correlating with increased expression of the epithelium-specific Trp63, a known transcriptional repressor of Klf4. The identified transcriptional cooperation between GR and Klf4 may determine cell-type specific regulation and have implications for developing therapies for skin diseases.
Description9 páginas, 5 figuras. En material suplementario: 2 tablas y 2 figuras
Publisher version (URL)http://dx.doi.org/10.1016/j.mce.2015.05.015
URIhttp://hdl.handle.net/10261/149408
DOI10.1016/j.mce.2015.05.015
ISSN0303-7207
E-ISSN1872-8057
Appears in Collections:(IBV) Artículos
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