AID targeting is dependent on RNA polymerase II pausing
1Department of Microbiology and Immunology, University of Illinois College of Medicine, 835 S. Wolcott, Chicago, IL 60612-7344, USA. star1@uic.edu
Seminars in Immunology
|July 13, 2012
Summary
Activation induced deaminase (AID) targets immunoglobulin loci, but its precise targeting rules remain unclear. Transcription-coupled events, including RNA polymerase II pausing, recruit AID to switch regions, explaining its targeting and mistargeting.
Area of Science:
- Immunology
- Molecular Biology
- Epigenetics
Background:
- Activation induced deaminase (AID) is crucial for adaptive immunity, mediating immunoglobulin gene diversification.
- AID targets specific DNA motifs within immunoglobulin loci, primarily switch (S) and variable (V) regions.
- The precise mechanisms governing AID targeting, including its potential off-target activity, are not fully understood.
Purpose of the Study:
- To elucidate the role of transcription in regulating Activation induced deaminase (AID) targeting to immunoglobulin loci.
- To investigate the unique features of S region transcription that influence AID recruitment.
- To understand the interplay between transcription, chromatin modifications, and AID targeting.
Main Methods:
- Analysis of S region transcription dynamics.
- Investigation of RNA polymerase II pausing.
- Assessment of chromatin remodeling and histone modifications.
- Studies on AID recruitment to targeted S regions.
Main Results:
- Transcription is essential for class switch recombination and somatic hypermutation.
- S region transcription involves RNA polymerase II pausing, which facilitates chromatin remodeling and histone modifications.
- These transcription-coupled events promote the recruitment of AID to targeted S regions.
- The study provides insights into both on-target and off-target AID activity.
Conclusions:
- Transcription-coupled events, particularly RNA polymerase II pausing in S regions, are key regulators of AID targeting.
- Understanding these mechanisms enhances our knowledge of AID's role in immunoglobulin gene regulation and potential off-target effects.
- This work clarifies the intricate relationship between transcription, chromatin state, and AID localization.
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