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| Status |
Public on Dec 22, 2020 |
| Title |
Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (ChIP-seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
B cell development is orchestrated by various transcription factors collaborating with chromatin remodelers that determine the genomic architecture. However, chromatin regulation in mature B cells is still poorly understood. Here, we show the critical function of positive coactivator 4 (PC4), a bona fide non-histone chromatin protein encoded by Sub1. B-cell specific Sub1-deficient mice showed the decreased number and response against antigen stimulation of mature B cells. By combining PC4 chromatin immunoprecipitation-sequencing and complex purification, we identified transcription factor IKAROS as a partner of PC4 in gene regulation. PC4 and IKAROS cooperated to promote heterochromatin formation of their target gene loci and thereby established B cell identity. Importantly, PC4 stabilized IKAROS protein in mature B cells and inhibited IKAROS degradation by the anti-cancer drug lenalidomide in human B-cell lymphoma cells. These findings establish PC4 as not only a chromatin regulator of B cells but also a new therapeutic target in B-cell malignancies.
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| |
|
| Overall design |
Function and regulation of PC4 in B cells
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| |
|
| Contributor(s) |
Ochiai K, Funayama R, Nakayama K, Igarashi K |
| Citation(s) |
33357426 |
| |
| Submission date |
Feb 26, 2020 |
| Last update date |
Mar 23, 2021 |
| Contact name |
Kyoko Ochiai |
| E-mail(s) |
kochiai@med.tohoku.ac.jp
|
| Organization name |
Tohoku University School of Medicine
|
| Department |
Biochemistry
|
| Street address |
2-1, Seiryo-machi, Aobaku
|
| City |
Sendai |
| ZIP/Postal code |
980-8575 |
| Country |
Japan |
| |
|
| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
|
| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE145953 |
Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 |
|
| Relations |
| BioProject |
PRJNA608863 |
| SRA |
SRP250793 |
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