Karki, S;
Kennedy, DE;
Mclean, K;
Grzybowski, AT;
Maienschein-Cline, M;
Banerjee, S;
Xu, H;
... Clark, MR; + view all
(2018)
Regulated Capture of Vκ Gene Topologically Associating Domains by Transcription Factories.
Cell Reports
, 24
(9)
pp. 2443-2456.
10.1016/j.celrep.2018.07.091.
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Abstract
Expression of vast repertoires of antigen receptors by lymphocytes, with each cell expressing a single receptor, requires stochastic activation of individual variable (V) genes for transcription and recombination. How this occurs remains unknown. Using single-cell RNA sequencing (scRNA-seq) and allelic variation, we show that individual pre-B cells monoallelically transcribe divergent arrays of Vκ genes, thereby opening stochastic repertoires for subsequent Vκ-Jκ recombination. Transcription occurs upon translocation of Vκ genes to RNA polymerase II arrayed on the nuclear matrix in transcription factories. Transcription is anchored by CTCF-bound sites or E2A-loaded Vκ promotors and continues over large genomic distances delimited only by topological associating domains (TADs). Prior to their monoallelic activation, Vκ loci are transcriptionally repressed by cyclin D3, which prevents capture of Vκ gene containing TADs by transcription factories. Cyclin D3 also represses protocadherin, olfactory, and other monoallelically expressed genes, suggesting a widely deployed mechanism for coupling monoallelic gene activation with cell cycle exit.
| Type: | Article |
|---|---|
| Title: | Regulated Capture of Vκ Gene Topologically Associating Domains by Transcription Factories |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2018.07.091 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2018.07.091 |
| Language: | English |
| Additional information: | © 2018 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Igκ repertoire, gene accessibility, gene accessibility, RNA polymerase II, CTCF, TADs, transcription factories, recombination center, germline transcription, monoallelic gene transcription |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10057227 |
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