A direct interaction between the RAG2 C terminus and the core histones is required for efficient V(D)J recombination.
V(D)J recombination is a tightly controlled process of somatic recombination whose regulation is mediated in part by chromatin structure. Here, we report that RAG2 binds directly to the core histone proteins. The interaction with histones is observed in developing lymphocytes and within the RAG1/RAG2 recombinase complex in a manner that is dependent on the RAG2 C terminus. Amino acids within the plant homeo domain (PHD)-like domain as well as a conserved acidic stretch of the RAG2 C terminus that is considered to be a linker region are important for this interaction. Point mutations that disrupt the RAG2-histone association inhibit the efficiency of the V(D)J recombination reaction at the endogenous immunoglobulin locus, with the most dramatic effect in the V to DJ(H) rearrangement.
West
Kelly L
KL
Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Singha
Netai C
NC
De Ioannes
Pablo
P
Lacomis
Lynne
L
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Cortes
Patricia
P
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D015321:Gene Rearrangement / Q000276:immunology*; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011817:Rabbits; D011995:Recombination, Genetic / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D045567:VDJ Recombinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D007136:Immunoglobulins; D009687:Nuclear Proteins; D010446:Peptide Fragments; C499309:RAG2 protein, Oryctolagus cuniculus; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D045567:VDJ Recombinases