Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Large intergenic non-coding RNAs as novel modulators of reprogramming: siRNA (gene expression)

ABSTRACT: lincRNA-ST8SIA3 was depleted using siRNAs and associated gene expression changes were profiled on Affymentrix arrays siRNAs targeting lincRNA-ST8SIA3 were transfected into human induced pluripotent stem cells; non-targeting siRNAs were used as controls GPL570 ;Affymetrix Human Genome U133 Plus 2.0 Array [Affy_HG-U133_Plus_2]

ORGANISM(S): Homo sapiens

SUBMITTER: Nataly Cabili

PROVIDER: E-GEOD-23973 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.

Loewer Sabine S Cabili Moran N MN Guttman Mitchell M Loh Yuin-Han YH Thomas Kelly K Park In Hyun IH Garber Manuel M Curran Matthew M Onder Tamer T Agarwal Suneet S Manos Philip D PD Datta Sumon S Lander Eric S ES Schlaeger Thorsten M TM Daley George Q GQ Rinn John L JL

Nature genetics 20101107 12

The conversion of lineage-committed cells to induced pluripotent stem cells (iPSCs) by reprogramming is accompanied by a global remodeling of the epigenome, resulting in altered patterns of gene expression. Here we characterize the transcriptional reorganization of large intergenic non-coding RNAs (lincRNAs) that occurs upon derivation of human iPSCs and identify numerous lincRNAs whose expression is linked to pluripotency. Among these, we defined ten lincRNAs whose expression was elevated in iP ...[more]

PMID: 21057500

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Project description:Recently, more than a thousand large intergenic non-coding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediated apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulating their localization to sets of previously active genes. Gene expression profiles of different p53 inducible mouse embryonic fibroblasts (p53LSL/LSL MEFs) across different time points after DNA damage. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 transcriptional response. [1] MEF profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration or adenoGFP as control for 24h and treated with 500nM doxorubicin for the indicated times. [2] hnRNPKKD profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration for 24h, transfected with siRNA oligos targeting different transcripts for 24h and then treated with 100nM doxorubicin for 13h. [3] lincP21KD profiling: p53 LSL/LSL MEFs were treated with adenoCRE for p53 restoration for 24h, transfected with siRNA oligos targeting different transcripts for 24h and then treated with 100nM doxorubicin for 13h. [4] RAS profiling: For p53 restoration, cultured tumor cell lines were incubated with 500nM 4-hydroxytamoxifen for the indicated times.

Dataset Information

Large intergenic non-coding RNAs as novel modulators of reprogramming: siRNA (gene expression)

Publications

Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells.

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