Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites.
Introduction of torsional stress into active chromatin domains requires that linear DNA molecules be anchored in vivo to impede free rotation. While searching for these anchorage elements, we have localized a nuclear matrix association region (MAR) within the mouse immunoglobulin kappa gene that contains two topoisomerase II sites and is adjacent to the tissue-specific enhancer. The same matrix contact occurs when the kappa locus is in germ-line (inactive) or rear-ranged (transcribed) configurations. This constitutive anchorage site partitions the gene into V-J and C region chromatin domains. We demonstrate that at least 10,000 similar and evolutionarily conserved MAR binding sites exist in the nucleus. We propose that these sites, in association with topoisomerase II and possibly in conjunction with enhancers, play fundamental roles in the functional organization of chromatin loop domains.
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure*; D002874:Chromosome Mapping; D002875:Chromosomes / Q000502:physiology / Q000648:ultrastructure*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D014018:Tissue Distribution; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D004250:DNA Topoisomerases, Type II