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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 13, 2020 |
| Title |
Smc3 regulates B-cell transit through germinal centers and restricts their malignant transformation (Mint-ChIP) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
During the germinal center (GC) reaction, B-cells undergo extensive redistribution of cohesin complex and 3D re-organization of their genomes. Yet, the significance of cohesin and architectural programming in the humoral immune response is unknown. Herein we report that conditional homozygous deletion of cohesin subunit Smc3 abrogated GC formation, yet in marked contrast, Smc3 haploinsufficiency induced GC hyperplasia, skewing of GC polarity and impaired plasma cell differentiation. Transcriptional and architectural profiling revealed defects in GC terminal differentiation programs controlled by lymphoma epigenetic tumor suppressors Tet2 and Kmt2d, and failure of Smc3+/- GC B-cells to switch from B-cell to plasma cell lineage factors. There was also impaired connectivity of gene regulatory elements controlling tumor suppressor genes, and accordingly Smc3 haploinsufficiency accelerated lymphomagenesis in mice with constitutive Bcl6 expression. Collectively, our data indicate a dose dependent function for cohesin in humoral immunity to facilitate the B-cell to plasma cell lineage switch, while restricting their malignant transformation.
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| Overall design |
Mint-ChIP sequencing was performed with 3 replicates of wild-type germinal center (GC) cells using H3K27Ac antibody (Cat#39133, lot 31814008) from Active Motif following the protocol from the Berstein lab.
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| Contributor(s) |
Rivas MA, Meydan C, Chin CR, Challman MF, Kim D, Binder B, Kloetgen A, Viny A, Teater M, McNally D, Doane AS, Béguelin W, Calvo Fernández MT, Shen H, Levine RL, Chen Z, Tsirigos A, Elemento O, Mason CE, Melnick AM |
| Citation(s) |
33432228 |
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| Submission date |
Mar 10, 2020 |
| Last update date |
Jan 19, 2021 |
| Contact name |
Cem Meydan |
| Organization name |
Weill Cornell Medical College
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| Department |
Physiology & Biophysics
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| Lab |
Melnick Lab & Mason Lab
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| Street address |
1305 York
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| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE143852 |
Smc3 regulates B-cell transit through germinal centers and restricts their malignant transformation |
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| Relations |
| BioProject |
PRJNA611813 |
| SRA |
SRP252254 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE146753_GC_WT_H3K27ac_mintchip_RPKM_smooth250_merged.bw |
179.2 Mb |
(ftp)(http) |
BW |
| GSE146753_Genrich_mintchip_GC_H3K27ac_WTSMC3_peaks.q001.narrowPeak.gz |
1.9 Mb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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