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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE145953 | GEO | 2020/12/22

REPOSITORIES: GEO

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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 (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 (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 (Agilent microarrays)

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

| PRJNA608862 | 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

Transcriptional coactivator PC4, a chromatin-associated protein, induces chromatin condensation.

Project description:Human transcriptional coactivator PC4 is a highly abundant multifunctional protein which plays diverse important roles in cellular processes, including transcription, replication, and repair. It is also a unique activator of p53 function. Here we report that PC4 is a bona fide component of chromatin with distinct chromatin organization ability. PC4 is predominantly associated with the chromatin throughout the stages of cell cycle and is broadly distributed on the mitotic chromosome arms in a punctate manner except for the centromere. It selectively interacts with core histones H3 and H2B; this interaction is essential for PC4-mediated chromatin condensation, as demonstrated by micrococcal nuclease (MNase) accessibility assays, circular dichroism spectroscopy, and atomic force microscopy (AFM). The AFM images show that PC4 compacts the 100-kb reconstituted chromatin distinctly compared to the results seen with the linker histone H1. Silencing of PC4 expression in HeLa cells results in chromatin decompaction, as evidenced by the increase in MNase accessibility. Knocking down of PC4 up-regulates several genes, leading to the G2/M checkpoint arrest of cell cycle, which suggests its physiological role as a chromatin-compacting protein. These results establish PC4 as a new member of chromatin-associated protein family, which plays an important role in chromatin organization.

| S-EPMC1636769 | biostudies-literature

Control of nutrient uptake by IRF4 orchestrates innate immune memory

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

2023-08-02 | GSE236556 | GEO

IL-4 orchestrates STAT6-mediated DNA demethylation leading to dendritic cell differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-12-12 | E-GEOD-75939 | biostudies-arrayexpress