biostudies-literatureMajumder KNIAID NIH HHSNCI NIH HHS107-20https://www.ebi.ac.uk/biostudies/studies/S-EPMC4291525biostudies-literatureUnknown212(1)Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containinThe Journal of experimental medicineLineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element.PMC4291525AI 081224R01 AI049934R21 AI081224F31 CA177086T32 AI052077R01 AI112621AI 49934CA177086R01 AI079732AI 079732R56 AI112621AI 112621Taniuchi IMajumder KOltz EMChan EABassing CHHorowitz JEKoues OIKyle KEKrangel MSYang-Iott KfalseLineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element.Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containin2015-01-01T00:00:00Z2015 Jan2026-05-02T21:15:02.012Z2019-03-27T01:43:17ZS-EPMC42915252551247010.1084/jem.20141479