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The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis

ABSTRACT: The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis

PROVIDER: PRJNA230532 | ENA |

REPOSITORIES: ENA

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The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [ChIP-seq]

Project description:The p53-regulated long non-coding RNA, lincRNA-p21, has been proposed to promote apoptosis and to repress in trans the expression of genes in the p53 transcriptional network. Here, we report the generation of a conditional knockout mouse model developed to further examine lincRNA-p21 function. Using this genetic approach, we find that the primary function of lincRNA-p21 is to activate in cis the expression of its neighboring gene, the cyclin-dependent kinase inhibitor p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a co-activator for p53-dependent transcription of p21. Additional phenotypes of lincRNA-p21 deficiency, including deregulated expression and altered chromatin state of a set of Polycomb target genes, defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency could be attributed to diminished p21 levels. This study reveals a novel paradigm, whereby the long non-coding RNA lincRNA-p21 affects global gene expression and influences events in the p53 tumor suppressor pathway by acting in cis as a locus-restricted transcriptional co-activator for p53-mediated expression of p21. Examination of 2 different histone modifications (H3K4me3 and H3K27me3) in 2 cell types (WT and lincRNA-p21 KO) in the presence and absence of Doxorubicin.

2014-05-22 | E-GEOD-52956 | biostudies-arrayexpress

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [RNA-seq]

Project description:The p53-regulated long non-coding RNA, lincRNA-p21, has been proposed to promote apoptosis and to repress in trans the expression of genes in the p53 transcriptional network. Here, we report the generation of a conditional knockout mouse model developed to further examine lincRNA-p21 function. Using this genetic approach, we find that the primary function of lincRNA-p21 is to activate in cis the expression of its neighboring gene, the cyclin-dependent kinase inhibitor p21. Mechanistically, we show that lincRNA-p21 acts in concert with hnRNP-K as a co-activator for p53-dependent transcription of p21. Additional phenotypes of lincRNA-p21 deficiency, including deregulated expression and altered chromatin state of a set of Polycomb target genes, defective G1/S checkpoint, increased proliferation rates, and enhanced reprogramming efficiency could be attributed to diminished p21 levels. This study reveals a novel paradigm, whereby the long non-coding RNA lincRNA-p21 affects global gene expression and influences events in the p53 tumor suppressor pathway by acting in cis as a locus-restricted transcriptional co-activator for p53-mediated expression of p21. mRNAseq in 2 cell types (WT and lincRNA-p21 KO) in the presence and absence of Doxorubicin performed in biological triplicate.

2014-05-22 | E-GEOD-52957 | biostudies-arrayexpress

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [RNA-seq]

2014-05-22 | GSE52957 | GEO

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis [ChIP-seq]

2014-05-22 | GSE52956 | GEO

LincRNA-p21 Blocks Somatic Cell Reprogramming by Sustaining H3K9me3 and CpG Methylation at Pluripotent Gene Promoters

Project description:Through expression profiling and functional screening we have identified the large intergenic non-coding RNA p21 (lincRNA-p21) as a barrier for reprogramming. LincRNA-p21 is induced by p53 but contrary to its role in the DNA damage response it does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase Setdb1 and the maintenance DNA methyltransferase Dnmt1 in separate complexes that are facilitated by the RNA binding protein hnRNP-K.

2014-12-29 | GSE57967 | GEO

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis

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

2014-05-22 | E-GEOD-52958 | biostudies-arrayexpress

The p53-regulated long noncoding RNA, lincRNA-p21 promotes the expression of Polycomb target genes and enforces the G1/S checkpoint by activating p21 in cis

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

2014-05-22 | GSE52958 | GEO

LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and to enforce the G1/S checkpoint.

Project description: Not available

| S-EPMC4103188 | biostudies-literature

Down-regulation of Polo-like kinase 4 (PLK4) induces G1 arrest via activation of the p38/p53/p21 signalling pathway in bladder

Project description:We demonstrate that Polo-like kinase 4(PLK4) is overexpressed in human bladder cancer (BC) cell lines and tissues, and its overexpression correlates with poor prognosis. PLK4 inhibition suppresses BC cell growth and induces G1 phase arrest via activating p38/p53/p21 pathway in vitro and in vivo. The data suggest that PLK4 might serve as a novel molecular target for BC treatment.

2021-07-29 | GSE180958 | GEO

PINT lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb Repressive Complex 2 (tissue)

Project description:It has been recently shown that the transcription factor p53 induces the expression of multiple lincRNAs. However, relatively little is known about the role that lincRNAs play in this pathway. Here we characterize a lincRNA named PINT (p53 Induced Noncoding Transcript). We show that PINT is a ubiquitously expressed lincRNA that is finely regulated by p53. In mouse cells, PINT promotes cell proliferation and survival by regulating the expression of genes of TGF-beta, MAPK and p53 pathways. PINT is a nuclear lincRNA that directly interacts with Polycomb Repressive Complex 2 (PRC2), being required for PRC2 targeting of specific genes for repression. Furthermore, PINT functional activity is dependent on PRC2 expression, representing a connection between the p53 pathway and epigenetic regulation by PRC2. We have also identified PINT human ortholog (hPINT), which presents suggestive analogies with the mouse lincRNA. hPINT is similarly regulated by p53, and its expression correlates significantly with the same cellular pathways as the mouse ortholog, including the p53 pathway. Interestingly, hPINT is significantly downregulated in colon cancer, representing a novel tumor suppressor candidate. Our results not only help our understanding of the role of p53 and lincRNAs in cancer, but also contribute to the open debate regarding the utility of mouse models for the study of lincRNAs.

2013-08-09 | GSE46271 | GEO

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