Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells.

Abstract

The aryl hydrocarbon receptor (AHR) is a transcription factor and environmental sensor that regulates expression of genes involved in drug-metabolism and cell cycle regulation. Chromatin immunoprecipitation analyses, Ahr ablation in mice and studies with orthologous genes in invertebrates suggest that AHR may also play a significant role in embryonic development. To address this hypothesis, we studied the regulation of Ahr expression in mouse embryonic stem cells and their differentiated progeny. In ES cells, interactions between OCT3/4, NANOG, SOX2 and Polycomb Group proteins at the Ahr promoter repress AHR expression, which can also be repressed by ectopic expression of reprogramming factors in hepatoma cells. In ES cells, unproductive RNA polymerase II binds at the Ahr transcription start site and drives the synthesis of short abortive transcripts. Activation of Ahr expression during differentiation follows from reversal of repressive marks in Ahr promoter chromatin, release of pluripotency factors and PcG proteins, binding of Sp factors, establishment of histone marks of open chromatin, and engagement of active RNAPII to drive full-length RNA transcript elongation. Our results suggest that reversible Ahr repression in ES cells holds the gene poised for expression and allows for a quick switch to activation during embryonic development.

• Authors: Chia-I Ko, Qin Wang, Yunxia Fan, Ying Xia, Alvaro Puga
• Journal: Stem cell research (Stem Cell Res) Vol. 12 Issue 1 Pg. 296-308 (Jan 2014) ISSN: 1876-7753 [Electronic] England
• PMID: 24316986 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Chromatin
• Histones
• Klf4 protein, mouse
• Kruppel-Like Factor 4
• Polycomb-Group Proteins
• Receptors, Aryl Hydrocarbon
• Transcription Factors
• Sp3 Transcription Factor
• RNA Polymerase II

Topics

• Animals
• Cell Differentiation
• Cells, Cultured
• Chromatin (metabolism)
• Embryonic Stem Cells (cytology, metabolism)
• Gene Expression Regulation
• Histones (metabolism)
• Kruppel-Like Factor 4
• Mice
• Mice, Inbred C57BL
• Phosphorylation
• Polycomb-Group Proteins (genetics, metabolism)
• Promoter Regions, Genetic
• Protein Binding
• RNA Polymerase II (metabolism)
• Receptors, Aryl Hydrocarbon (genetics, metabolism)
• Sp3 Transcription Factor
• Transcription Factors (genetics, metabolism)
• Transcription Initiation Site