Here, we investigated the potential interaction between bromodomain-containing protein 4 (BRD4), an established epigenetic modulator and transcriptional coactivator, and p63, a member of the p53 transcription factor family, essential for epithelial development and skin homeostasis. Our protein–protein interaction assays demonstrated a strong and conserved physical interaction between BRD4 and the p53 family members—p63, p73, and p53—suggesting a shared binding region among these proteins. While the role of BRD4 in cancer development through its interaction with p53 has been explored, the effects of BRD4 and Bromodomain and Extra Terminal (BET) inhibitors in non-transformed cells, such as keratinocytes, remain largely unknown. Our functional analyses revealed changes in cellular proliferation and differentiation in keratinocytes depleted of either p63 or BRD4, which were further supported by using the BRD4 inhibitor JQ1. Transcriptomic analyses, chromatin immunoprecipitation, and RT-qPCR indicated a synergistic mechanism between p63 and BRD4 in regulating the transcription of keratinocyte-specific p63 target genes, including HK2, FOXM1, and EVPL. This study not only highlights the complex relationship between BRD4 and p53 family members but also suggests a role for BRD4 in maintaining keratinocyte functions. Our findings pave the way for further exploration of potential therapeutic applications of BRD4 inhibitors in treating skin disorders.

E. Foffi

A. Violante

R. Pecorari

A. M. Lena

F. Rugolo

G. Melino

E. Candi

Biology Direct

BIOLOGY DIRECT 作为开放获取、同行评审的在线期刊服务于生命科学研究社区，为作者和读者提供了传统同行评审模式的替代方案。 BIOLOGY DIRECT 考虑目前被认为最有利于开放审查方法的学科领域的原创研究文章、假设、评论、发现笔记和评论，主要是那些具有重要非实验成分的领域。

Biology Direct is an open-access, peer-reviewed online journal that serves the life sciences research community. It provides authors and readers with an alternative to the traditional peer review model. Biology Direct considers original research articles, hypotheses, reviews, discovery notes, and commentaries, particularly in fields that are currently viewed as most conducive to open review methods.

《Biology Direct》是一份开放获取、同行评审的在线期刊，旨在服务于生命科学研究社区。它为作者和读者提供了一种传统同行评审模式的替代方案。《Biology Direct》接受原创研究文章、假设、评论、发现笔记和评论，特别关注那些具有重要非实验成分的学科领域。

Category	Quartile
生物学	2
生物学, 生物学	2

BRD4 sustains p63 transcriptional program in keratinocytes

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