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Status |
Public on Jan 20, 2023 |
Title |
A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination [Micro-C] |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Antibody class switch recombination (CSR) requires the ligation of DNA breaks in transcribed and juxtaposed donor and acceptor switch (S) sequences (S-S synapsis) spaced 50-200 kb apart within the immunoglobulin heavy chain locus (Igh). CSR is believed to occur via the association of active S regions with the 3’ regulatory region (3’RR) super-enhancer thereby coupling transcription with S-S synapsis. Here, we map the multi-way interactome underlying CSR using Tri-C. Surprisingly, S-S synapsis is strongly associated with the 3` CTCF binding element (3`CBE), but not the 3’RR, a finding also confirmed by Micro-C measurements. Instead, the 3’RR forms a self-interacting domain independently engaging with Igh genes. Additionally, transcription at acceptor S regions creates a topological barrier that insulates S-S synapsis from loop extrusion complexes. Thus, Igh gene activation and S-S synapsis occur via distinct topological states created by the interaction between transcription and the loop extrusion machinery.
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Overall design |
Examination of the multi-way interactome at the Igh locus through Micro-C.
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Web link |
https://pubmed.ncbi.nlm.nih.gov/36736317/
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Contributor(s) |
Costea J, Schoeberl UE, Malzl D, von der Linde M, Fitz J, Goloborodko A, Pavri R |
Citation(s) |
36736317 |
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Submission date |
Mar 09, 2022 |
Last update date |
Apr 24, 2023 |
Contact name |
Maximilian Christian von der Linde |
E-mail(s) |
maximilian.linde@imp.ac.at, max_vdl@outlook.com
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Phone |
+4368181646556
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Organization name |
Institute of Molecular Pathology
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Lab |
Pavri GRP
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Street address |
Campus-vienna-biocenter 1, IMP, Pavri GRP
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City |
Vienna |
State/province |
Vienna |
ZIP/Postal code |
1030 |
Country |
Austria |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (2) |
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This SubSeries is part of SuperSeries: |
GSE198182 |
A de novo transcription-dependent TAD boundary underpins critical multiway interactions during antibody class switch recombination |
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Relations |
BioProject |
PRJNA814068 |