An autoregulatory loop directs the tissue-specific expression of p63 through a long-range evolutionarily conserved enhancer

Dario Antonini, Barbara Rossi, Rong Han, Annunziata Minichiello, Tina Di Palma, Marcella Corrado, Sandro Banfi, Mariastella Zannini, Janice L. Brissette, Caterina Missero

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

p63, a p53 family member, is essential for the development of various stratified epithelia and is one of the earliest markers of many ectodermal structures, including the epidermis, oral mucosa, apical ectodermal ridge, and mammary gland. Genetic regulatory mechanisms controlling p63 spatial expression during development have not yet been defined. Using a genomic approach, we identified an evolutionarily conserved cis-regulatory element, located 160 kb downstream of the first p63 exon, which functions as a keratinocyte-specific enhancer and is sufficient to recapitulate expression of the endogenous gene during mouse embryogenesis. Dissection of the p63 enhancer activity revealed a positive autoregulatory loop in which the p63 proteins directly bind to and are essential regulators of the enhancer. Accordingly, transactivating p63 isoforms induce endogenous p63 expression in cells that do not normally express this gene, whereas dominant negative isoforms suppress p63 expression in keratinocytes. In addition the transcription factor AP-2 also binds to the enhancer and cooperates with p63 to induce its activity. These results demonstrate that a long-range autoregulatory loop is involved in the regulation of p63 expression during embryonic development and in adult cells.

Original languageEnglish
Pages (from-to)3308-3318
Number of pages11
JournalMolecular and Cellular Biology
Volume26
Issue number8
DOIs
Publication statusPublished - Apr 2006

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Keratinocytes
Embryonic Development
Protein Isoforms
Transcription Factor AP-2
Dominant Genes
Mouth Mucosa
Human Mammary Glands
Epidermis
Dissection
Exons
Epithelium
Gene Expression
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

An autoregulatory loop directs the tissue-specific expression of p63 through a long-range evolutionarily conserved enhancer. / Antonini, Dario; Rossi, Barbara; Han, Rong; Minichiello, Annunziata; Di Palma, Tina; Corrado, Marcella; Banfi, Sandro; Zannini, Mariastella; Brissette, Janice L.; Missero, Caterina.

In: Molecular and Cellular Biology, Vol. 26, No. 8, 04.2006, p. 3308-3318.

Research output: Contribution to journalArticle

Antonini, D, Rossi, B, Han, R, Minichiello, A, Di Palma, T, Corrado, M, Banfi, S, Zannini, M, Brissette, JL & Missero, C 2006, 'An autoregulatory loop directs the tissue-specific expression of p63 through a long-range evolutionarily conserved enhancer', Molecular and Cellular Biology, vol. 26, no. 8, pp. 3308-3318. https://doi.org/10.1128/MCB.26.8.3308-3318.2006
Antonini, Dario ; Rossi, Barbara ; Han, Rong ; Minichiello, Annunziata ; Di Palma, Tina ; Corrado, Marcella ; Banfi, Sandro ; Zannini, Mariastella ; Brissette, Janice L. ; Missero, Caterina. / An autoregulatory loop directs the tissue-specific expression of p63 through a long-range evolutionarily conserved enhancer. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 8. pp. 3308-3318.
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