The 3D structure of the immunoglobulin heavy-chain locus: Implications for long-range genomic interactions

S Jhunjhunwala, Menno van Zelm, MM Peak, S Cutchin, R Riblet, Jacques Dongen, Frank Grosveld, Tobias Knoch, C Murre

Research output: Contribution to journalArticleAcademicpeer-review

223 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)265-279
Number of pages15
JournalCell
Volume133
Issue number2
DOIs
Publication statusPublished - 2008

Cite this