TY - JOUR
T1 - Tprg, a gene predominantly expressed in skin, is a direct target of the transcription factor p63
AU - Antonini, Dario
AU - Dentice, Monica
AU - Mahtani, Parvesh
AU - De Rosa, Laura
AU - Gatta, Giusy Della
AU - Mandinova, Anna
AU - Salvatore, Domenico
AU - Stupka, Elia
AU - Missero, Caterina
PY - 2008/7
Y1 - 2008/7
N2 - p63 and p73 are highly homologous members of the p53 family that originated by gene duplication at the invertebrate-to-vertebrate transition. We characterize here a previously unreported gene, Transformation-related protein 63 regulated (Tprg), located upstream of the p63 gene in the vertebrate genome, with striking similarity to Transformation related protein 63 regulated like (Tprgl), an uncharacterized gene located upstream of p73, suggesting that p63/Tprg and p73/Tprgl are embedded in a paralogue region originated from a single duplication event. Tprg is predominantly expressed in the epithelial compartment of the skin, more abundantly in differentiated cells. Consistent with its relative higher expression in differentiated keratinocytes, finely tuned p63 expression levels are required for optimal Tprg expression in primary keratinocytes. p63 is essential for Tprg expression as shown in p63-knockdown keratinocytes; however, high levels of p63 result in Tprg downregulation. p63 directly binds in vivo to a canonical p63-binding site in an evolutionary conserved genomic region located in Tprg intron 4. This genomic region is sufficient to function as a p63-inducible enhancer in promoter studies. Thus, we demonstrate that the Tprg gene is predominantly expressed in skin, is physically associated with the p63 gene during evolution, and directly regulated by p63 through a long-distance enhancer located within the Tprg locus.
AB - p63 and p73 are highly homologous members of the p53 family that originated by gene duplication at the invertebrate-to-vertebrate transition. We characterize here a previously unreported gene, Transformation-related protein 63 regulated (Tprg), located upstream of the p63 gene in the vertebrate genome, with striking similarity to Transformation related protein 63 regulated like (Tprgl), an uncharacterized gene located upstream of p73, suggesting that p63/Tprg and p73/Tprgl are embedded in a paralogue region originated from a single duplication event. Tprg is predominantly expressed in the epithelial compartment of the skin, more abundantly in differentiated cells. Consistent with its relative higher expression in differentiated keratinocytes, finely tuned p63 expression levels are required for optimal Tprg expression in primary keratinocytes. p63 is essential for Tprg expression as shown in p63-knockdown keratinocytes; however, high levels of p63 result in Tprg downregulation. p63 directly binds in vivo to a canonical p63-binding site in an evolutionary conserved genomic region located in Tprg intron 4. This genomic region is sufficient to function as a p63-inducible enhancer in promoter studies. Thus, we demonstrate that the Tprg gene is predominantly expressed in skin, is physically associated with the p63 gene during evolution, and directly regulated by p63 through a long-distance enhancer located within the Tprg locus.
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U2 - 10.1038/jid.2008.12
DO - 10.1038/jid.2008.12
M3 - Article
C2 - 18256694
AN - SCOPUS:45349102059
VL - 128
SP - 1676
EP - 1685
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 7
ER -