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A stepwise epigenetic process controls immunoglobulin allelic exclusion.
Yehudit Bergman1, Howard Cedar
1Department of Experimental Medicine, Hebrew University Medical School, Ein Kerem, Jerusalem 91120, Israel.
Nature Reviews. Immunology
|October 2, 2004
Summary
During T and B cell differentiation, epigenetic repression is removed to allow immune receptor gene rearrangement. This process, called allelic exclusion, may also generate gene diversity in other biological systems.
Area of Science:
- Immunology
- Epigenetics
- Genomics
Background:
- Immune receptor gene rearrangement is crucial for T and B cell differentiation.
- Steric accessibility of immune-receptor loci is a prerequisite for gene rearrangement.
Purpose of the Study:
- To discuss the epigenetic mechanisms enabling immune-receptor gene accessibility.
- To propose a novel role for allelic exclusion in generating gene diversity.
Main Methods:
- Review of epigenetic repression mechanisms (replication timing, heterochromatization, histone acetylation, DNA methylation).
- Analysis of stepwise removal of these mechanisms during cell differentiation.
Main Results:
- Epigenetic repression is stepwise removed to grant steric accessibility to immune-receptor loci.
- This process initially favors one allele within each cell, establishing allelic exclusion.
Conclusions:
- The described epigenetic regulation facilitates immune receptor gene rearrangement.
- Allelic exclusion may be a conserved mechanism for generating genetic diversity across different biological systems.