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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 30, 2022 |
| Title |
Nuclear corepressors NCOR1/NCOR2 regulate B cell development, maintain genomic integrity, and prevent transformation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The nuclear corepressors NCOR1 and NCOR2 interact with transcription factors involved in B cell development and potentially link these factors to alterations in chromatin structure and gene expression. Herein we demonstrate that NCOR1/2 deletion limits B cell differentiation via impaired recombination, attenuates pre-BCR-signaling, and enhances STAT5-dependent transcription. Furthermore, NCOR1/2-deficient B cells exhibited derepression of EZH2-repressed gene modules, including the p53 pathway. These alterations resulted in aberrant Rag1 and Rag2 expression and accessibility in proliferating cells. Whole-genome sequencing of Ncor1/2 DKO B cells identified increased number of structural variants compared to wildtype B cells with cryptic recombination signal sequences. Finally, deletion of Ncor1 alleles in mice facilitated leukemic transformation, while human leukemias with less NCOR1 correlated with worse survival. NCOR1 mutations in human leukemia correlated with increased RAG expression and increased number of structural variants. These studies illuminate how the corepressors NCOR1/2 regulate B cell differentiation and provide insights into how NCOR1/2 mutations may promote B cell transformation.
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| Overall design |
scATAC-Seq and scRNA-Seq WT, Ncor1-KO, Ncor1_Ncor2-DKO
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| Contributor(s) |
Lee RD, Knutson TP, Munro SA, Miller J, Heltemes-Harris LM, Jepsen K, Farrar MA |
| Citation(s) |
36316474 |
| Submission date |
Jul 20, 2022 |
| Last update date |
Jan 05, 2023 |
| Contact name |
Todd P Knutson |
| E-mail(s) |
knut0297@umn.edu
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| Phone |
612-626-8911
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| Organization name |
University of Minnesota
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| Department |
Minnesota Supercomputing Institute
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| Street address |
117 Pleasant St SE
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| City |
Minneapolis |
| State/province |
MN |
| ZIP/Postal code |
55455 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| GSM6360702 |
ADT_WT_rep1&2_Ncor1KO_rep_1&2, Ncor1&2DKO_rep1&2 |
| GSM6360703 |
GEX_WT_rep1&2_Ncor1KO_rep_1&2, Ncor1&2DKO_rep1&2 |
| GSM6360704 |
HTO_WT_rep1&2_Ncor1KO_rep_1&2, Ncor1&2DKO_rep1&2 |
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| Relations |
| BioProject |
PRJNA860565 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE208656_RAW.tar |
3.3 Gb |
(http)(custom) |
TAR (of MTX, TXT) |
| GSE208656_scATACseq_barcodes_DKO.txt.gz |
33.3 Kb |
(ftp)(http) |
TXT |
| GSE208656_scATACseq_barcodes_KO.txt.gz |
23.9 Kb |
(ftp)(http) |
TXT |
| GSE208656_scATACseq_barcodes_WT.txt.gz |
34.2 Kb |
(ftp)(http) |
TXT |
| GSE208656_scATACseq_features.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE208656_scATACseq_metadata_DKO.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
| GSE208656_scATACseq_metadata_KO.txt.gz |
933.3 Kb |
(ftp)(http) |
TXT |
| GSE208656_scATACseq_metadata_WT.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
| GSE208656_singlecell_adt_features.txt.gz |
145 b |
(ftp)(http) |
TXT |
| GSE208656_singlecell_cell_metadata.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
| GSE208656_singlecell_gex_features.txt.gz |
332.7 Kb |
(ftp)(http) |
TXT |
| GSE208656_singlecell_hto_features.txt.gz |
119 b |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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