GRHL3/GET1 and trithorax group members collaborate to activate the epidermal progenitor differentiation program

PLoS Genet. 2012;8(7):e1002829. doi: 10.1371/journal.pgen.1002829. Epub 2012 Jul 19.

Abstract

The antagonistic actions of Polycomb and Trithorax are responsible for proper cell fate determination in mammalian tissues. In the epidermis, a self-renewing epithelium, previous work has shown that release from Polycomb repression only partially explains differentiation gene activation. We now show that Trithorax is also a key regulator of epidermal differentiation, not only through activation of genes repressed by Polycomb in progenitor cells, but also through activation of genes independent of regulation by Polycomb. The differentiation associated transcription factor GRHL3/GET1 recruits the ubiquitously expressed Trithorax complex to a subset of differentiation genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • DNA Methylation
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Epidermal Cells
  • Epidermis / metabolism
  • Epithelial Cells* / cytology
  • Epithelial Cells* / metabolism
  • Gene Expression Regulation, Developmental
  • Histone-Lysine N-Methyltransferase* / genetics
  • Histone-Lysine N-Methyltransferase* / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Myeloid-Lymphoid Leukemia Protein / metabolism
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Polycomb-Group Proteins / genetics
  • Polycomb-Group Proteins / metabolism
  • Promoter Regions, Genetic
  • RNA, Small Interfering
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Transglutaminases / genetics
  • Transglutaminases / metabolism

Substances

  • DNA-Binding Proteins
  • GRHL3 protein, human
  • Intracellular Signaling Peptides and Proteins
  • KMT2A protein, human
  • KMT2D protein, human
  • Neoplasm Proteins
  • Polycomb-Group Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • WDR5 protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • Transglutaminases
  • transglutaminase 1
  • Calcium

Associated data

  • GEO/GSE37049
  • GEO/GSE37570
  • GEO/GSE38628