C/EBPδ gene targets in human keratinocytes

• Published in: PloS one 2010-11, Vol.5 (11), p.e13789-e13789
• Main Authors: Borrelli, Serena, Fanoni, Daniele, Dolfini, Diletta, Alotto, Daniela, Ravo, Maria, Grober, Olì Maria Victoria, Weisz, Alessandro, Castagnoli, Carlotta, Berti, Emilio, Vigano, M Alessandra, Mantovani, Roberto
• Format: Article
• Language: English
• Subjects: Adipocytes; Apoptosis; Basal cell carcinoma; Basal cells; Blotting, Western; Cancer; CCAAT-Enhancer-Binding Protein-delta - genetics; CCAAT-Enhancer-Binding Protein-delta - metabolism; Cell Differentiation; Cell growth; Cells, Cultured; Cytokines; Deactivation; Dermatology/Skin Cancers, including Melanoma and Lymphoma; Developmental Biology/Cell Differentiation; Differentiation; Epidermis; Epigenetics; Fibroblasts; Gene expression; Gene Expression Profiling; Genes; Genetics and Genomics/Functional Genomics; Genetics and Genomics/Gene Expression; Genotype & phenotype; Growth factors; Homeostasis; Humans; Immunohistochemistry; Inactivation; Interferon; Keratinocytes; Keratinocytes - cytology; Keratinocytes - metabolism; Leukemia; MafB Transcription Factor - genetics; MafB Transcription Factor - metabolism; Molecular Biology/Transcription Initiation and Activation; Oligonucleotide Array Sequence Analysis; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; siRNA; Skin; Skin - metabolism; Skin - pathology; Skin cancer; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Squamous cell carcinoma; Stem cells; Target recognition; Tissue Array Analysis; Tissues; Transcription factors; Tumorigenesis; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013789

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.