KLF3 Mediates Epidermal Differentiation through the Epigenomic Writer CBP
Jackson Jones,
Yifang Chen,
Manisha Tiwari,
Jingting Li,
Ji Ling,
George L. Sen
Affiliations
Jackson Jones
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
Yifang Chen
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
Manisha Tiwari
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
Jingting Li
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
Ji Ling
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
George L. Sen
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; Corresponding author
Summary: 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.
