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High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
Published on: February 7, 2019
Multiple transcription factor binding sites predict AID targeting in non-Ig genes
Jamie L Duke1, Man Liu, Gur Yaari
1Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 22, 2013
Summary
Activation-induced cytidine deaminase (AID) mistargeting causes mutations in germinal center B cells. This study identifies transcription factor binding sites that recruit AID, aiding in predicting its genomic targets.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Aberrant targeting of activation-induced cytidine deaminase (AID) leads to somatic mutations in approximately 25% of expressed genes in germinal center B cells.
- Evidence suggests that many genes efficiently repair AID-induced DNA lesions, implying that up to 45% of genes might be targeted by AID.
- Understanding AID recruitment mechanisms is crucial as mistargeting poses a significant risk for genome instability.
Purpose of the Study:
- To investigate the mechanisms responsible for recruiting AID to specific gene loci.
- To identify common properties shared by AID target genes.
- To develop a predictive model for AID targeting across the genome.
Main Methods:
- Analysis of 7.3 Mb of sequence data and regulatory context from 83 genes in Ung(-/-) Msh2(-/-) mice.
- Identification of common properties of AID targets.
- Development of a classification tree model to predict AID targeting based on identified features and prior knowledge.
Main Results:
- Identification of three key transcription factor binding sites (E-box motifs, YY1, and C/EBP-β) that may cooperate to recruit AID.
- Construction of a predictive model for genome-wide AID targeting.
- Identification of 101 high-interest genes predicted to be AID targets.
Conclusions:
- Multiple mechanisms likely collaborate to target AID to specific genomic loci.
- Transcription factor binding sites play a critical role in recruiting AID.
- The developed predictive model can identify potential high-risk AID targets, aiding further research into genome instability and B cell mutations.
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