TY - JOUR
T1 - The 3D Structure of the Immunoglobulin Heavy-Chain Locus
T2 - Implications for Long-Range Genomic Interactions
AU - Jhunjhunwala, Suchit
AU - van Zelm, Menno C.
AU - Peak, Mandy M.
AU - Cutchin, Steve
AU - Riblet, Roy
AU - van Dongen, Jacques J.M.
AU - Grosveld, Frank G.
AU - Knoch, Tobias A.
AU - Murre, Cornelis
PY - 2008/4/18
Y1 - 2008/4/18
N2 - The immunoglobulin heavy-chain (Igh) locus is organized into distinct regions that contain multiple variable (VH), diversity (DH), joining (JH) and constant (CH) 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 VH, DH, JH, and CH elements, showed compartmentalization and striking conformational changes involving VH and DH-JH elements during early B cell development. In pro-B cells, the entire repertoire of VH regions (2 Mbp) appeared to have merged and juxtaposed to the DH elements, mechanistically permitting long-range genomic interactions to occur with relatively high frequency.
AB - The immunoglobulin heavy-chain (Igh) locus is organized into distinct regions that contain multiple variable (VH), diversity (DH), joining (JH) and constant (CH) 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 VH, DH, JH, and CH elements, showed compartmentalization and striking conformational changes involving VH and DH-JH elements during early B cell development. In pro-B cells, the entire repertoire of VH regions (2 Mbp) appeared to have merged and juxtaposed to the DH elements, mechanistically permitting long-range genomic interactions to occur with relatively high frequency.
KW - CELLBIO
KW - DNA
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=41949121201&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2008.03.024
DO - 10.1016/j.cell.2008.03.024
M3 - Article
C2 - 18423198
AN - SCOPUS:41949121201
SN - 0092-8674
VL - 133
SP - 265
EP - 279
JO - Cell
JF - Cell
IS - 2
ER -