The transcription factor p63 regulates epidermal genes and the enhancer landscape in skin keratinocytes. Its molecular function in controlling the chromatin structure is, however, not yet completely understood. Here, we integrated multi-omics profiles, including the transcriptome, transcription factor DNA-binding and chromatin accessibility, in skin keratinocytes isolated from EEC syndrome patients carrying p63 mutations, to examine the role of p63 in shaping the chromatin architecture. We found decreased chromatin accessibility in p63- and CTCF-bound open chromatin regions that potentially contributed to gene deregulation in mutant keratinocytes. Cooperation of p63 and CTCF seemed to assist chromatin interactions between p63-bound enhancers and gene promoters in skin keratinocytes. Our study suggests an intriguing model where cell type-specific transcription factors such as p63 cooperate with the genome organizer CTCF in the three-dimensional chromatin space to regulate the transcription program important for the proper cell identity.

中文翻译：

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p63与CTCF协同调节皮肤角质形成细胞中的染色质结构。

转录因子p63调节皮肤角质形成细胞中的表皮基因和增强子景观。然而，其在控制染色质结构中的分子功能尚不完全清楚。在这里，我们整合了多组学概况，包括从带有p63突变的EEC综合征患者中分离出的皮肤角质形成细胞中的转录组，转录因子DNA结合和染色质可及性，以检查p63在塑造染色质结构中的作用。我们发现p63和CTCF绑定的开放染色质区域中的染色质可及性降低，这可能导致突变型角质形成细胞中的基因失调。p63和CTCF的合作似乎有助于皮肤角质形成细胞中p63结合的增强子和基因启动子之间的染色质相互作用。