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PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins

ABSTRACT: PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins

PROVIDER: PRJNA835849 | ENA |

REPOSITORIES: ENA

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PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins

Project description:The cell cycle is an intensively control process, in which cell-cycle proteins display a cyclical expression pattern regulated by specific transcription, translation and degradation. Cell cycle progression is initiated by highly expressed D-type cyclins (D1/2/3) to facilitate DNA synthesis, subsequently driven by mitotic proteins formation (e.g., centromere proteins) that is responsible for mitosis onset. Whether there exist master regulators to keep the cycle rapidly “running” with D-type cyclins induction, as well as maintain the cycle in a stable process by centromere proteins modulation is of particular interest yet remains unclear at present. Here our study clarifies human positive cofactor 4 (PC4) as a previously unrecognized RNA binding protein (RBP), as a post-transcriptional master regulator to orchestrate CCND1 and CENPF expression. We reveal that lack of PC4 reduces CCND1 stability whereas enhances excessive CENPF translation, results in cell cycle arrest and mitotic defects. Furthermore, PC4 RNA binding activity is strictly controlled by S17 phosphorylation and K68 ubiquitination in a cell cycle-dependent way. Lastly, we use in vivo model to verify that PC4 deficiency amplifies response of cancer cells to CDK4/6 inhibitor, and PC4 induction accelerates liver regeneration after partial hepatectomy. These results highlight that cell-cycle gene expressions are dynamically and post-transcriptionally fine-tuned, and identify PC4 as an essential cell-cycle post-transcriptional manipulator that is profoundly applied within cancer and regeneration medicine.

2024-02-03 | PXD033637 | Pride

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RIP-Seq).

Project description:PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RIP-Seq).

| PRJNA835853 | ENA

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (eCLIP-Seq).

Project description:PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (eCLIP-Seq).

| PRJNA835851 | ENA

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RNA-Seq).

Project description:PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RNA-Seq).

| PRJNA835854 | ENA

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (eCLIP-Seq).

Project description:To investigate the binding site in which PC4 protein association with its target RNAs. eCLIP-seq was performed to profile PC4-binding RNA targets in Huh7 cells.

2024-02-12 | GSE202400 | GEO

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RIP-Seq).

Project description:To investigate the mRNA targets of PC4 that worked as an RNA binding protein to control cell cycle progression. RIP-seq was displayed to profile PC4-binding RNA targets in Huh7 cells.

2024-02-12 | GSE202399 | GEO

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RNA-Seq).

Project description:To investigate the downstream targets of PC4 in controlling cell cycle, we knockdowned PC4 with two different siRNAs in Huh7 cells. We performed RNA-seq in Huh7 cells transfected with NC, siPC4-1 or siPC4-2.

2024-02-12 | GSE202397 | GEO

PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins

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

2024-02-11 | GSE202401 | 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

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

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