GRHL3 binding and enhancers rearrange as epidermal keratinocytes transition between functional states
Year: 2017
Type: article
Abstract: Transcription factor binding, chromatin modifications and large scale chromatin re-organization underlie progressive, irreversible cell lineage commitments and differentiation. We know little, however, about chromatin changes as cells enter transient, reversible states such as migration. Here we demonstrate that when human progenitor keratinocytes either differentiate or migrate they form complements of typical enhancers and super-enhancers that are unique for each state. Unique super-enhancers for each cellular state link to gene expression that confers functions associated with the respective cell state. These super-enhancers are also enriched for skin disease sequence variants. GRHL3, a transcription factor that promotes both differentiation and migration, binds preferentially to super-enhancers in differentiating keratinocytes, while during migration, it binds preferentially to promoters along with REST, repressing the expression of migration inhibitors. Key epidermal differentiation transcription factor genes, including GRHL3, are located within super-enhancers, and many of these transcription factors in turn bind to and regulate super-enhancers. Furthermore, GRHL3 represses the formation of a number of progenitor and non-keratinocyte super-enhancers in differentiating keratinocytes. Hence, chromatin relocates GRHL3 binding and enhancers to regulate both the irreversible commitment of progenitor keratinocytes to differentiation and their reversible transition to migration.
Source: PLoS Genetics
Authors: Rachel Herndon Klein, Ziguang Lin, Amelia Soto Hopkin, William Gordon, Lam C. Tsoi, Yun Liang, Johann E. Gudjonsson, Bogi Andersen
Institutions: University of California, Irvine, University of Michigan
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: Arthritis National Research Foundation, Dermatology Foundation, National Psoriasis Foundation, A. Alfred Taubman Medical Research Institute, National Research Foundation, National Institutes of Health, University of California, Irvine, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G2502927309, Institute for Clinical and Translational Science, Training Program in Systems Biology of Development, Role of IL-13 and the IL-13 Associated rs20541 Risk Variant in the Pathogenesis of Psoriasis, G9000329045, Training Grant in Cell and Molecular Dermatology, Transcriptional Co-Regulators in Epidermis
OpenAlex ID: W2609050486