Transcription factor p63 bookmarks and regulates dynamic enhancers during epidermal differentiation

Abstract: 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.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Transcription factor p63 bookmarks and regulates dynamic enhancers during epidermal differentiation ; volume:16 ; number:7 ; year:2015 ; pages:863-878 ; extent:16
EMBO reports / European Molecular Biology Organization ; 16, Heft 7 (2015), 863-878 (gesamt 16)

Creator
Kouwenhoven, Evelyn N.
Oti, Martin
Niehues, Hanna
van Heeringen, Simon J.
Schalkwijk, Joost
Stunnenberg, Hendrik G.
van Bokhoven, Hans
Zhou, Huiqing

DOI
10.15252/embr.201439941
URN
urn:nbn:de:101:1-2022112305010958825723
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:36 AM CEST

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Associated

  • Kouwenhoven, Evelyn N.
  • Oti, Martin
  • Niehues, Hanna
  • van Heeringen, Simon J.
  • Schalkwijk, Joost
  • Stunnenberg, Hendrik G.
  • van Bokhoven, Hans
  • Zhou, Huiqing

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