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Trithorax Genes in the Control of Keratinocyte Differentiation

  • Rachel Herndon Klein
  • Bogi AndersenEmail author
Chapter
  • 372 Downloads
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Developmental processes involved in the initial morphogenesis, tissue homeostasis, and repair of skin require precisely controlled levels of gene expression at specific times and locations. This balance is accomplished through the concerted and antagonistic efforts of tissue-specific transcriptional regulators interacting with the chromatin landscape, epigenetic-modifying enzymes, and noncoding RNAs. While activating Trithorax and repressing Polycomb complexes represent a classic example of antagonistic epigenetic regulation during early development, their roles in gene regulation extend beyond this capacity. Since the divergence of flies and mammals, the Trithorax family of SET enzymes has expanded greatly, taking on new and largely non-redundant roles, creating a complex regulatory milieu that can integrate diverse sets of signals into a single transcriptional program in each cell type. In contrast to Polycomb complex members, the Trithorax complex is highly expressed across the differentiation stages of epidermal keratinocytes. The specificity of epigenetic targeting is accomplished through interactions of chromatin modifying complexes with lineage specific transcription factors such as GRHL3, leading to selective activation of the proper gene expression program at each stage of differentiation. Additionally, evidence from studies in the epidermis suggests that these enzymes can also act independently of Polycomb to activate gene expression in the absence of repressive chromatin.

Keywords

Trithorax Polycomb Epigenetic regulation WDR5 GRHL3 histone methylation Epidermal differentiation 

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Authors and Affiliations

  1. 1.Departments of Biological Chemistry and MedicineUniversity of CaliforniaIrvineUSA

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