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oai:repisalud.isciii.es:20.500.12105/272472026-02-20T21:23:03Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Lopez, Rodolphe G author Garcia-Silva, Susana author Moore, Susan J author Bereshchenko, Oksana author Martinez-Cruz, Ana B author Ermakova, Olga author Kurz, Elke author Paramio, Jesus M author Nerlov, Claus author 2009-10 The transcriptional regulators that couple interfollicular basal keratinocyte proliferation arrest to commitment and differentiation are yet to be identified. Here we report that the basic region leucine zipper transcription factors C/EBPalpha and C/EBPbeta are co-expressed in basal keratinocytes, and are coordinately upregulated as keratinocytes exit the basal layer and undergo terminal differentiation. Mice lacking both C/EBPalpha and beta in the epidermis showed increased proliferation of basal keratinocytes and impaired commitment to differentiation. This led to ectopic expression of keratin 14 (K14) and DeltaNp63 in suprabasal cells, decreased expression of spinous and granular layer proteins, parakeratosis and defective epidermal water barrier function. Knock-in mutagenesis revealed that C/EBP-E2F interaction was required for control of interfollicular epidermis (IFE) keratinocyte proliferation, but not for induction of spinous and granular layer markers, whereas C/EBP DNA binding was required for DeltaNp63 downregulation and K1/K10 induction. Finally, loss of C/EBPalpha/beta induced stem cell gene expression signatures in the epidermis. C/EBPs, therefore, couple basal keratinocyte cell cycle exit to commitment to differentiation through E2F repression and DNA binding, respectively, and may act to restrict the epidermal stem cell compartment. Nat Cell Biol . 2009 Oct;11(10):1181-90. Nature Cell Biology 19749746 https://hdl.handle.net/20.500.12105/27247 CCAAT/ENHANCER-BINDING PROTEINSTRANSCRIPTION FACTORS -C/EBP STEM CELL GENES EXPRESION BARRIER FUNCTION HAIR FOLLICLE LIGASE ITCHIN-VIVOSKINP63 IN-VIVO SKIN P63 C/EBPalpha and beta couple interfollicular keratinocyte proliferation arrest to commitment and terminal differentiation.