Localized Epigenetic Changes Induced by DH Recombination Restricts Recombinase to DJH Junctions
| Autor: | Frederick W. Alt, Irina Ivanova, David G. Schatz, Yanhong Ji, Tirtha Chakraborty, Hansen Du, Ramesh Subrahmanyam, Ranjan Sen, Yu Zhang |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Genes
Immunoglobulin Heavy Chain Immunology Gene Rearrangement B-Lymphocyte Heavy Chain Immunoglobulin Variable Region chemical and pharmacologic phenomena Biology Germline Article Cell Line Epigenesis Genetic Histones Recombinases Mice Recombinase Immunology and Allergy Recombination signal sequences Animals Gene Immunoglobulin Joining Region Genetics Recombination Genetic B-Lymphocytes Precursor Cells B-Lymphoid Chromatin Immunoglobulin heavy chain Immunoglobulin Heavy Chains Recombination |
| Zdroj: | Nature immunology |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | Genes encoding immunoglobulin heavy chains (Igh) are assembled by rearrangement of variable (V(H)), diversity (D(H)) and joining (J(H)) gene segments. Three critical constraints govern V(H) recombination. These include timing (V(H) recombination follows D(H) recombination), precision (V(H) gene segments recombine only to DJ(H) junctions) and allele specificity (V(H) recombination is restricted to DJ(H)-recombined alleles). Here we provide a model for these universal features of V(H) recombination. Analyses of DJ(H)-recombined alleles showed that DJ(H) junctions were selectively epigenetically marked, became nuclease sensitive and bound RAG recombinase proteins, which thereby permitted D(H)-associated recombination signal sequences to initiate the second step of Igh gene assembly. We propose that V(H) recombination is precise, because these changes did not extend to germline D(H) segments located 5' of the DJ(H) junction. |
| Databáze: | OpenAIRE |
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