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Series GSE214869 Query DataSets for GSE214869
Status Public on May 01, 2023
Title Enhancers of the PAIR4 regulatory module promote distal VH gene recombination at the Igh locus
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary While extended loop extrusion across the entire Igh locus controls VH-DJH recombination, local regulatory sequences, such as the PAIR elements, may also activate VH gene recombination in pro-B-cells. Here we show that PAIR-associated VH8 genes contain a conserved putative regulatory element (V8E) in their downstream sequences. To investigate the function of PAIR4 and its V8.7E, we deleted all 14 PAIRs in the Igh 5’-region, which reduced distal VH gene recombination over a 100-kb distance on either side of the 890-kb deletion. Reconstitution by insertion of PAIR4-V8.7E strongly activated distal VH gene recombination. PAIR4 alone resulted in lower induction of recombination, indicating that PAIR4 and V8.7E function as one regulatory unit. The pro-B-cell-specific activity of PAIR4 depends on CTCF, as mutation of its CTCF-binding site led to sustained PAIR4 activity in pre-B and immature B-cells and in PAIR4 activation in T-cells. Notably, insertion of V8.8E was sufficient to activate VH gene recombination. Hence, enhancers of the PAIR4-V8.7E module and V8.8E element activate distal VH gene recombination and thus contribute to the diversification of the BCR repertoire in addition to loop extrusion.
Overall design VDJ-Seq: Nine experimental conditions, with three biological replicates each, associated with control samples (Igh(+/+)). RNA-Seq: two control (Igh(_delta_890/+) and two experimental (Igh(P4V/P4V)) samples. total RNA-Seq: two control samples. ChIP-Seq: Four control samples, single replcates.
Contributor(s) Hill L, Jaritz M, Schindler K, Tagoh H, Kostanova-Poliakova D, Sun Q, Schwickert TA, Leeb M, Skarnes WC, Busslinger M
Citation(s) 37337907
Submission date Oct 05, 2022
Last update date Jul 31, 2023
Contact name Meinrad Busslinger
Organization name IMP
Lab Busslinger
Street address Campus-Vienna-Biocenter 1
City Vienna
ZIP/Postal code A-1030
Country Austria
Platforms (5)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (59)
GSM6617040 187484
GSM6617041 196279
GSM6617042 9592
BioProject PRJNA887428

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Supplementary file Size Download File type/resource
GSE214869_RAW.tar 1.6 Gb (http)(custom) TAR (of BW, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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