Transcription factor p63 bookmarks and regulates dynamic enhancers during epidermal differentiation
Publication year
2015Author(s)
Number of pages
16 p.
Source
EMBO Reports, 16, 7, (2015), pp. 863-78ISSN
Publication type
Article / Letter to editor
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Organization
Human Genetics
Dermatology
Molecular Biology
Molecular Developmental Biology
Journal title
EMBO Reports
Volume
vol. 16
Issue
iss. 7
Languages used
English (eng)
Page start
p. 863
Page end
p. 78
Subject
Molecular Biology; Radboudumc 10: Reconstructive and regenerative medicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 5: Inflammatory diseases RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience; Molecular Developmental BiologyAbstract
The transcription factor p63 plays a pivotal role in keratinocyte proliferation and differentiation in the epidermis. However, how p63 regulates epidermal genes during differentiation is not yet clear. Using epigenome profiling of differentiating human primary epidermal keratinocytes, we characterized a catalog of dynamically regulated genes and p63-bound regulatory elements that are relevant for epithelial development and related diseases. p63-bound regulatory elements occur as single or clustered enhancers, and remarkably, only a subset is active as defined by the co-presence of the active enhancer mark histone modification H3K27ac in epidermal keratinocytes. We show that the dynamics of gene expression correlates with the activity of p63-bound enhancers rather than with p63 binding itself. The activity of p63-bound enhancers is likely determined by other transcription factors that cooperate with p63. Our data show that inactive p63-bound enhancers in epidermal keratinocytes may be active during the development of other epithelial-related structures such as limbs and suggest that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates genes through temporal- and spatial-specific active enhancers.
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