Cutting edge: developmental stage-specific recruitment of cohesin to CTCF sites throughout immunoglobulin loci during B lymphocyte development.
Contraction of the large Igh and Igkappa loci brings all V genes, spanning >2.5 Mb in each locus, in proximity to DJ(H) or J(kappa) genes. CCCTC-binding factor (CTCF) is a transcription factor that regulates gene expression by long-range chromosomal looping. We therefore hypothesized that CTCF may be crucial for the contraction of the Ig loci, but no CTCF sites have been described in any V loci. Using ChIP-chip, we demonstrated many CTCF sites in the V(H) and V(kappa) regions. However, CTCF enrichment in the Igh locus, but not the Igkappa locus, was largely unchanged throughout differentiation, suggesting that CTCF binding alone cannot be responsible for stage-specific looping. Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci. The differential binding of cohesin to CTCF sites may promote multiple loop formation and thus effective V(D)J recombination.
Degner
Stephanie C
SC
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Wong
Timothy P
TP
Jankevicius
Gytis
G
Feeney
Ann J
AJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000235:genetics / Q000276:immunology; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015322:Gene Rearrangement, B-Lymphocyte; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000378:metabolism*; D000097722:Cohesins
D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D000097722:Cohesins; C000619698:Ctcf protein, mouse; C465862:Rad21 protein, mouse