title: The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions.
abstract: The immunoglobulin heavy-chain (Igh) locus is organized into distinct regions that contain multiple variable (V(H)), diversity (D(H)), joining (J(H)) and constant (C(H)) coding elements. How the Igh locus is structured in 3D space is unknown. To probe the topography of the Igh locus, spatial distance distributions were determined between 12 genomic markers that span the entire Igh locus. Comparison of the distance distributions to computer simulations of alternative chromatin arrangements predicted that the Igh locus is organized into compartments containing clusters of loops separated by linkers. Trilateration and triple-point angle measurements indicated the mean relative 3D positions of the V(H), D(H), J(H), and C(H) elements, showed compartmentalization and striking conformational changes involving V(H) and D(H)-J(H) elements during early B cell development. In pro-B cells, the entire repertoire of V(H) regions (2 Mbp) appeared to have merged and juxtaposed to the D(H) elements, mechanistically permitting long-range genomic interactions to occur with relatively high frequency.
authors.affiliation: Division of Biological Sciences, 0377, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Suchit
authors.initials: S
authors.lastname: Jhunjhunwala
authors.forename: Menno C
authors.initials: MC
authors.lastname: van Zelm
authors.forename: Mandy M
authors.initials: MM
authors.lastname: Peak
authors.forename: Steve
authors.initials: S
authors.lastname: Cutchin
authors.forename: Roy
authors.initials: R
authors.lastname: Riblet
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: Frank G
authors.initials: FG
authors.lastname: Grosveld
authors.forename: Tobias A
authors.initials: TA
authors.lastname: Knoch
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D050438:Genes, Immunoglobulin Heavy Chain; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D050441:VDJ Exons