C/EBPs are a family of B-Zip transcription factors -TFs- involved in the regulation of differentiation in several tissues. The two most studied members -C/EBPα and C/EBPβ- play important roles in skin homeostasis and their ablation reveals cells with stem cells signatures. Much less is known about C/EBPδ which is highly expressed in the granular layer of interfollicular epidermis and is a direct target of p63, the master regular of multilayered epithelia. We identified C/EBPδ target genes in human primary keratinocytes by ChIP on chip and profiling of cells functionally inactivated with siRNA. Categorization suggests a role in differentiation and control of cell-cycle, particularly of G2/M genes. Among positively controlled targets are numerous genes involved in barrier function. Functional inactivation of C/EBPδ as well as overexpressions of two TF targets -MafB and SOX2- affect expression of markers of keratinocyte differentiation. We performed IHC on skin tumor tissue arrays: expression of C/EBPδ is lost in Basal Cell Carcinomas, but a majority of Squamous Cell Carcinomas showed elevated levels of the protein. Our data indicate that C/EBPδ plays a role in late stages of keratinocyte differentiation.
C/EBPd gene targets in human keratinocytes / S. Borrelli, D. Fanoni, D. Dolfini, D. Alotto, M. Ravo, O.M.V. Grober, A. Weisz, C. Castagnoli, E. Berti, M..A. Vigano, R. Mantovani. - In: PLOS ONE. - ISSN 1932-6203. - 5:11(2010), pp. e13789.1-e13789.12.
|Titolo:||C/EBPd gene targets in human keratinocytes|
BORRELLI, SERENA (Corresponding)
MANTOVANI, ROBERTO (Corresponding)
|Parole Chiave:||binding-protein-delta; mammary epithelial-cells; breast-cancer; 1,25-dihydroxyvitamin D-3; transcription factors; skin tumorigenesis; Netherton-syndrome; human epidermis; deficient mice; hair follicle|
|Settore Scientifico Disciplinare:||Settore MED/35 - Malattie Cutanee e Veneree|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1371/journal.pone.0013789|
|Appare nelle tipologie:||01 - Articolo su periodico|