PC4 is a post-transcriptional manipulator of D-type cyclins and centromere proteins (RIP-Seq).
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE202399 | GEO | 2024/02/12
REPOSITORIES: GEO
Similar Datasets
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
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
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
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
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-02-11 | GSE202401 | GEO
Project description:Radiotherapy is one of the mainstays for the treatment of hepatocellular carcinoma (HCC); however, a substantial fraction of HCC patients develops radioresistance and eventually suffer from tumour progression or relapse, a major impediment to the use of radiotherapy. One of the main goals in HCC management is to elucidate the mechanisms underlying radioresistance and identify novel therapeutic targets to improve the patients' prognosis. In this study, we report a DNA repair enhancer, human positive cofactor 4 (PC4), that promotes NHEJ-based DNA repair and renders HCC cells resistant to radiation. Mechanistically, PC4 interacts with PARP1 and directs Ku complex PARylation, resulting in successful recruitment of the Ku complex to damaged chromatin and increasing the efficiency of NHEJ repair. Clinically, PC4 is highly expressed in tumour tissues, which is correlated with poor prognosis in HCC patients. Taken together, our data suggest that PC4 is a DNA repair driver that can be targeted to radiosensitize HCC.
2023-10-24 | PXD042218 | Pride
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
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
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 | GSE145951 | GEO
Project description:Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. SSCs express key OSKM reprogramming factors at some levels, and do not require ectopic expression of any gene for the acquisition of pluripotency during reprogramming to mSSCs. Therefore, we reasoned that additional factors are required to regulate SSC reprogramming. In this study, we first compared the expression of reprogramming signature genes among somatic cells, iPSC, SSCs, mSSCs, and partially reprogramed cells, and found that they appear to have similar pluripotency states, whereas their transcriptional program differs. We developed a systems biology approach to prioritise genes for pluripotency regulatory factors by integrating transcriptome and interactome data on the genome-wide functional network. Then, we performed a series of systematic gene prioritisation steps and identified 53 candidates, which included some known reprogramming factors. We experimentally validated one particular candidate, Positive cofactor 4 (Pc4), which was expressed in PSCs and yielded a positive RNA interference (RNAi) response in an Oct4 reporter assay. We demonstrated that Pc4 enhanced the efficiency of OSKM-mediated reprogramming by promoting the transcriptional activity of key pluripotency factors, and by regulating the expression of many protein- and miRNA-encoding genes involved in reprogramming and somatic cell-specific genes. Pc4-overexpressing mESC lines were established by Venus (YFP)-expressing lentiviral transfection. The mESCs were split at a density of 2 ´ 104 cells onto fresh MEF feeder cells seeded into a 6 well dish (containing mESC growth medium) with virus particles, and 25 μg/ml polybrene (Sigma Aldrich) was added. After 24 h, the medium was replaced with fresh growth medium. After 4 days later, mESC colonies expressing YFP were picked and replated. Three different Pc4-overexpressing mESC lines were established.
2015-10-30 | E-GEOD-74149 | biostudies-arrayexpress