2026-08-30T21:25:59Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/272472026-02-20T21:23:03Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991
Repisalud
author
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
2026-02-20T21:23:03Z
2026-02-20T21:23:03Z
2009-10
Nat Cell Biol . 2009 Oct;11(10):1181-90.
Nature Cell Biology
19749746
https://hdl.handle.net/20.500.12105/27247
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.
eng
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.
research article
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