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KLF3 Promotes Human Epidermal Differentiation Through the Epigenomic Writer CBP and the Epigenomic Reader BRD4

Abstract

Human epidermis acts as an essential barrier between the body and the outside environment. It is a stratified epithelium that requires a proper balance of cell proliferation and differentiation to maintain its homeostasis and integrity. Stem and progenitor cells in the basal layer of the epidermis maintain a population of proliferative cells while also giving rise to differentiated progeny. Those cells entering the differentiation program undergo various stages of differentiation as they migrate outwards through the epidermis, where they will eventually form the protective outer layer known as the stratum corneum. As this process occurs, a variety of genes become expressed or repressed depending on the process of differentiation. Coordination of this differential gene expression between the stem/progenitor state and the differentiated state is a complex process that continues to undergo extensive investigation. Here, we identify and characterize KLF3 as a novel epidermal LDTF necessary for epidermal differentiation. In addition, we demonstrate that KLF3 promotes differentiation gene expression by promoting the localization of the epigenomic writer CBP and the epigenomic reader BRD4 at enhancers proximal to epidermal differentiation genes.

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