Jones Jackson, Chen Yifang, Tiwari Manisha, Li Jingting, Ling Ji, Sen George L
Department of Dermatology, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0869, USA.
Department of Dermatology, Department of Cellular and Molecular Medicine, UCSD Stem Cell Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0869, USA.
iScience. 2020 Jul 24;23(7):101320. doi: 10.1016/j.isci.2020.101320. Epub 2020 Jun 29.
Impairments in the differentiation process can lead to skin diseases that can afflict ∼20% of the population. Thus, it is of utmost importance to understand the factors that promote the differentiation process. Here we identify the transcription factor KLF3 as a regulator of epidermal differentiation. Knockdown of KLF3 results in reduced differentiation gene expression and increased cell cycle gene expression. Over half of KLF3's genomic binding sites occur at active enhancers. KLF3 binds to active enhancers proximal to differentiation genes that are dependent upon KLF3 for expression. KLF3's genomic binding sites also highly overlaps with CBP, a histone acetyltransferase necessary for activating enhancers. Depletion of KLF3 causes reduced CBP localization at enhancers proximal to differentiation gene clusters, which leads to loss of enhancer activation but not priming. Our results suggest that KLF3 is necessary to recruit CBP to activate enhancers and drive epidermal differentiation gene expression.
分化过程中的损伤会导致皮肤病，约20%的人口会受其影响。因此，了解促进分化过程的因素至关重要。在这里，我们确定转录因子KLF3是表皮分化的调节因子。敲低KLF3会导致分化基因表达减少和细胞周期基因表达增加。KLF3超过一半的基因组结合位点出现在活性增强子处。KLF3与依赖KLF3表达的分化基因附近的活性增强子结合。KLF3的基因组结合位点也与CBP高度重叠，CBP是激活增强子所必需的组蛋白乙酰转移酶。KLF3的缺失导致CBP在分化基因簇附近的增强子处定位减少，这导致增强子激活丧失但不影响起始。我们的结果表明，KLF3是招募CBP以激活增强子并驱动表皮分化基因表达所必需的。
