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Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (Agilent microarrays)

ABSTRACT: Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (Agilent microarrays)

PROVIDER: PRJNA608862 | ENA |

REPOSITORIES: ENA

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Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (Agilent microarrays)

Project description: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.

2020-12-22 | GSE145952 | GEO

Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (RRBS)

Project description:Chromatin protein positive coactivator 4 (PC4) has multiple functions, including chromatin compaction. However, its role in immune cells is largely unknown. We show that PC4 orchestrates chromatin structure and gene expression in mature B cells. B-cell specific PC4-deficient mice showed impaired production of antibody upon antigen stimulation. The PC4 complex purified from B cells contained transcription factors IKAROS and IRF4. IKAROS protein was reduced in PC4-deficient mature B cells, resulting in de-repression of their target genes in part by diminished interactions with gene silencing components. Upon activation, IRF4 protein amount was not increased in PC4-deficient B cells, resulting in reduction of plasma cells. Importantly, IRF4 reciprocally induced PC4 expression via a super-enhancer. PC4 knockdown in human B-cell lymphoma cells reduced IKAROS protein as an anticancer drug lenalidomide. Our findings establish PC4 as a chromatin regulator of B cells and a possible therapeutic target adjoining IKAROS in B-cell malignancies.

2020-12-22 | GSE163216 | GEO

Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (ChIP-seq)

2020-12-22 | GSE145951 | GEO

Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4

Project description:Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4

| PRJNA608861 | ENA

Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (RRBS)

Project description:Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (RRBS)

| PRJNA685217 | ENA

Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (ChIP-seq)

Project description:Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4 (ChIP-seq)

| PRJNA608863 | ENA

Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF4

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-22 | GSE145953 | GEO

Genome-wide DNA accessibility mapping using ATAC-seq in HEK293 in vector control, PC4 knockdown and PC4 phosphorylation specific mutant and mimic

Project description:To assess the mechanisms by which PC4 mediates chromatin compaction in cells and regulation of genome organization by its phosphorylation state, we measured the chromatin accessibility landscape using ATAC-seq of vector control 293 cells (Control/shNS), PC4 knockdown (KD/PC4 KD) and upon ectopic expression of Flag tagged PC4 (FP/PC4), Phosphomimic-PC4 (PM/PM-PC4) and phospho-mutant (MTP/MTP5) in PC4 knockdown cells.

2022-05-12 | GSE191333 | GEO

Myeloma IRF4 target genes - Agilent

Project description:The goal of this gene expression study was to identify genes whose expression depends on the transription factor IRF4 by knocking down it's expression using shRNA in two IRF4+ myeloma cell lines. Keywords: time series design Two myeloma lines were analyzed over a time course of IRF4-targeted shRNA induction. There are 3 time courses: two using KMS12 (biological replicates) and one with SKMM1. Within each time course there are technical replicates.

2010-05-26 | E-GEOD-9067 | biostudies-arrayexpress

Myeloma IRF4 target genes - Agilent

2008-07-07 | GSE9067 | GEO

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