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Updated: May 12, 2026
12:54
Real-time Analysis of Transcription Factor Binding, Transcription, Translation, and Turnover to Display Global Events During Cellular Activation
Published on: March 7, 2018
Analysis of sequence variation underlying tissue-specific transcription factor binding and gene expression.
Karen M Lower1, Marco De Gobbi, Jim R Hughes
1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Human Mutation
|April 26, 2013
Summary
Common DNA variants in noncoding regions significantly alter gene expression by affecting transcription factor binding. This variation in gene regulation may explain individual susceptibility to complex genetic diseases.
Area of Science:
- Genetics
- Molecular Biology
- Genomics
Background:
- Monogenic disorders stem from mutations in specific genes.
- Complex disorders are often linked to variations in noncoding DNA regions.
- These noncoding variants influence gene expression, leading to cell-specific or allele-specific differences.
Purpose of the Study:
- To investigate the mechanisms by which noncoding DNA sequence variation affects gene expression.
- To study natural variation in transcription factor (TF) binding during erythropoiesis.
Main Methods:
- Utilized a purified cell system of erythropoiesis to study TF binding.
- Analyzed common polymorphisms and their impact on TF binding sites.
- Investigated the effect of single nucleotide polymorphisms (SNPs) on multiprotein complex recruitment and chromatin modification.
Main Results:
- Common polymorphisms were found to directly perturb TF binding sites.
- These perturbations led to significant (~10-fold) changes in allele-specific, tissue-specific gene expression.
- SNPs distant from TF binding sites can alter multiprotein complex recruitment and chromatin modifications.
Conclusions:
- Common sequence variations in noncoding regions can directly alter tissue-specific gene expression.
- These mechanisms provide insight into how genetic variation influences susceptibility to complex human diseases.
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