Deconstructing lincRNA regulation during ESC to NPC differentiation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE107493 | GEO | 2018/08/01
REPOSITORIES: GEO
Similar Datasets
Project description:Deconstructing lincRNA regulation during ESC to NPC differentiation
| PRJNA420368 | ENA
Project description:There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. While there are some well-characterized examples, the vast majority (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here, we report a new approach to identifying large non-coding RNAs (ncRNAs) by using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified ~1600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening ncRNAs (lincRNAs) exhibit strong purifying selection in their genomic loci, exonic sequences, and promoter regions – with greater than 95% showing clear evolutionary conservation. We also developed a novel functional genomics approach that assigns putative functions to each lincRNA, revealing a diverse range of roles for lincRNAs in processes from ES pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFKB, Sox2, Oc4, and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes. lincRNA expression patterns were generated across a compendium of mouse tissues, cell types, and conditions. lincRNA expression profiles were generated on custom NimbleGen arrays (Samples GSM346609..GSM346650) and correlated with known protein coding genes on Affymetrix gene expression arrays (Samples GSM347910..GSM347943).
2009-01-01 | E-GEOD-13765 | biostudies-arrayexpress
Project description:Long intergenic noncoding RNAs (lincRNAs) are critical regulators involved in diverse biological processes. However, the roles and related mechanisms of lincRNAs in axon development are largely unknown. To seek the axon-enriched lincRNAs in DRG neurons, we performed high-throughput RNA-seq of cultured rat dorsal root ganglion (DRG) neurons at P0 to profile lincRNAs. Profiling of highly expressed lincRNAs in RNA-seq and their enrichment in the axon of DRG neurons. We report a previously unappreciated axon-enriched lincRNA regulating axon elongation, thus referred to as ALAE. ALAE functionally associates with KHSRP for preventing KHSRP binding on Gap43 mRNA, thereby maintaining GAP43 synthesis and facilitating axon elongation.
2023-06-02 | GSE151615 | GEO
Project description:There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. While there are some well-characterized examples, the vast majority (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise. Here, we report a new approach to identifying large non-coding RNAs (ncRNAs) by using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified ~1600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening ncRNAs (lincRNAs) exhibit strong purifying selection in their genomic loci, exonic sequences, and promoter regions – with greater than 95% showing clear evolutionary conservation. We also developed a novel functional genomics approach that assigns putative functions to each lincRNA, revealing a diverse range of roles for lincRNAs in processes from ES pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFKB, Sox2, Oc4, and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.
2009-01-01 | GSE13765 | GEO
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. Normal tissue located at least 20 cm away from a tumor was obtained through surgical resection from patients of colorectal cancer. Total RNA was extracted and subjected to microarray analysis.
2013-08-09 | E-GEOD-46271 | biostudies-arrayexpress
Project description:It has become clear that long intergenic noncoding RNAs (lincRNAs) are an important layer of genome regulation. Thousands have been identified in mammals, yet only a few have been tested through genetic ablation in animal models. Of the few that have, many yields weak to unobservable phenotypes, raising the question of their in vivo relevance. To more broadly investigate the functional relevance of lincRNAs in physiological conditions, we developed a collection of 18 lincRNA knockout strains. We found that two knockout strains, linc-Sox2 and linc-Foxf1a (Fendrr), exhibit perinatal lethal phenotypes in addition to multiple developmental abnormalities. Notably, in depth analysis of a third mutant strain, linc-Brn1b-/-, revealed defects in brain development, with distinct abnormalities in class-specific generation of upper layer II/III-IV neurons in the neocortex. Thus far, we found at least 6 of 18 mutant strains exhibit distinct developmental or lethality phenotypes. Therefore, this study demonstrates that lincRNAs are required for life and play critical roles during mammalian development, highlighting the importance of studying them further to better understand the molecular mechanisms leading to disease. Minimum 2 replicates each of select wild type and lincRNA knockout embryonic and postnatal tissues for three distinct lincRNA knockout mouse strains.
2013-11-30 | E-GEOD-49581 | biostudies-arrayexpress
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
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 | GSE46247 | GEO
Project description:Long intergenic noncoding RNAs (lincRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lincRNAs and bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of two lincRNAs reveal that RNA binding sites in the genome are focal, sequence-specific, and numerous. Human telomerase RNA TERC occupies telomeres and Wnt pathway genes. HOTAIR lincRNA preferentially binds a GA-rich homopurine DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. HOTAIR occupancy occurs independently of EZH2, defining the order of RNA guidance of Polycomb occupancy. ChIRP-seq is readily applicable to numerous RNAs in different cell types and biological states, thus enabling the study of RNA regulation of chromatin and gene expression at a genomic scale. Examination of 3 lincRNAs in 5 cell types
2011-09-29 | E-GEOD-31332 | biostudies-arrayexpress
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. Inhibition of PINT or p53 gene expression and subsequent treatment with 150 nM doxorubicine for 12h in MEF LSL p53 +/+ cells.
2013-08-09 | E-GEOD-46247 | biostudies-arrayexpress