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p63 directly induces expression of Alox12, a regulator of epidermal barrier formation
Author(s) -
Kim Soeun,
Choi Irene F.,
Quante Jessica R.,
Zhang Lei,
Roop Dennis R.,
Koster Maranke I.
Publication year - 2009
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2009.00894.x
Subject(s) - regulator , microbiology and biotechnology , master regulator , chemistry , biology , transcription factor , biochemistry , gene
Epidermal development and differentiation are tightly controlled processes that culminate in the formation of the epidermal barrier. A critical regulator of different stages of epidermal development and differentiation is the transcription factor p63. More specifically, we previously demonstrated elsewhere that p63 is required for both the commitment to stratification and the commitment to terminal differentiation. We now demonstrate that ΔNp63α, the predominantly expressed p63 isoform in postnatal epidermis, also plays a role in the final stages of epidermal differentiation, namely the formation of the epidermal barrier. We found that ΔNp63α contributes to epidermal barrier formation by directly inducing expression of ALOX12, a lipoxygenase which contributes to epidermal barrier function. Our data demonstrate that ΔNp63α directly interacts with the promoter of Alox12 in the developing epidermis. Furthermore, we found that the induction of Alox12 expression by ΔNp63α depends on intact p63 binding sites in the Alox12 promoter. Finally, we found that ΔNp63α can induce Alox12 expression only in differentiating keratinocytes, consistent with the role of ALOX12 in epidermal barrier formation.