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Updated: Nov 18, 2025
Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Enhancers predominantly regulate gene expression during differentiation via transcription initiation
Martin S C Larke1, Ron Schwessinger1, Takayuki Nojima2
1MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Gene expression control during cell differentiation primarily relies on altering transcription initiation, not RNA polymerase II (Pol II) pausing. Transcriptional enhancers play a key role in regulating this initiation process.
Area of Science:
- Molecular Biology
- Genetics
- Gene Regulation
Background:
- Gene transcription involves initiation, pausing, and elongation by RNA polymerase II (Pol II).
- Understanding how transcriptional enhancers control gene expression is crucial.
Purpose of the Study:
- To evaluate the role of transcriptional enhancers in gene expression control during differentiation.
- To determine whether gene expression changes are driven by initiation or Pol II pausing.
Main Methods:
- A combinatorial approach to assess promoter-proximal transcription (initiation and pausing) genome-wide.
- Utilized genetically engineered mouse models with deleted α- and β-globin enhancers.
Main Results:
- Gene expression during differentiation is mainly controlled by changes in transcription initiation, not Pol II pausing release.
- Deletion of specific enhancers confirmed their role in regulating Pol II recruitment and initiation.
- Enhancers modulate gene expression by affecting RNA polymerase II (Pol II) recruitment and initiation.
Conclusions:
- Transcriptional regulation during cell differentiation predominantly occurs at the initiation step.
- Transcriptional enhancers are critical regulators of gene initiation and expression control.
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