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The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [1]

ABSTRACT: Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of Dali, a conserved central nervous system expressed intergenic lncRNA. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein. Dali interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes.

ORGANISM(S): Mus musculus

PROVIDER: GSE62031 | GEO | 2014/12/03

SECONDARY ACCESSION(S): PRJNA262985

REPOSITORIES: GEO

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The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [3]

Project description:Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of Dali, a conserved central nervous system expressed intergenic lncRNA. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein. Dali interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes. N2A cells transfected with a non-targeting control vector were compared to N2A cells transfected with a Pou3f3 knockdown construct. Three biological replicates of each condition were analysed on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

2014-12-03 | E-GEOD-62033 | biostudies-arrayexpress

The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [1]

Project description:Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of Dali, a conserved central nervous system expressed intergenic lncRNA. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein. Dali interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes. N2A cells transfected with a non-targeting control vector were compared to N2A cells transfected with a Dali knockdown construct. Three biological replicates of each condition were analysed on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

2014-12-03 | E-GEOD-62031 | biostudies-arrayexpress

The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [2]

2014-12-03 | GSE62032 | GEO

The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [4]

2014-12-03 | GSE62034 | GEO

The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [3]

2014-12-03 | GSE62033 | GEO

The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [2]

Project description:Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of Dali, a conserved central nervous system expressed intergenic lncRNA. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein. Dali interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes. Proliferating and retinoic acid (RA-) differentiated N2A cells stably transfected with a non-targeting (scrambled) control vector were compared to proliferating and RA-differentiated N2A cells stably transfected with a Dali knockdown construct. Three biological replicates of each cell type and condition were analysed on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

2014-12-03 | E-GEOD-62032 | biostudies-arrayexpress

The DNMT1 associated lncRNA Dali is an epigenetic regulator of neural differentiation [4]

Project description:Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of Dali, a conserved central nervous system expressed intergenic lncRNA. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein. Dali interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes. The genome-wide binding profile of Dali was determined using Capture Hybridisation Analysis of RNA Targets (CHART)-Seq technique (Simon et al, Proc Natl Acad Sci U S A 108: 20497-20502, 2011) in N2A cells. Following the CHART-seq protocol, we used RNase H elution to recover genomic DNA associated with endogenous Dali transcripts. We identified Dali binding sites in comparison both to an input DNA sample from N2A cells and to DNA recovered using the control E.coli LacZ oligonucleotide. Please note that n2a_input, n2a_LacZ data was published previously [GSE52571]

2014-12-03 | E-GEOD-62034 | biostudies-arrayexpress

Leuciscus waleckii isolate:Dali Nor Lake

Project description:Leuciscus waleckii isolate:Dali Nor Lake Raw sequence reads

| PRJNA924546 | ENA

The long non-coding RNA Paupar regulates the expression of both local and distal genes [Paupar KD]

Project description:Although some long noncoding RNAs (lncRNAs) have been shown to regulate gene expression in cis, it remains unclear whether lncRNAs can directly regulate transcription in trans by interacting with chromatin genome-wide independently of their sites of synthesis. Here, we describe the genomically local and more distal functions of Paupar, a vertebrate-conserved and central nervous system-expressed lncRNA transcribed from a locus upstream of the gene encoding the Pax6 transcription factor. Knockdown of Paupar disrupts the normal cell cycle profile of neuroblastoma cells and induces neuronal differentiation. Paupar acts in a transcript-dependent manner both locally, to regulate Pax6, as well as distally by binding and regulating genes on multiple chromosomes, in part through physical association with Pax6 protein. Paupar binding sites are enriched near promoters and can function as transcriptional regulatory elements whose activity is modulated by Paupar transcript levels. Our findings demonstrate that a lncRNA can function in trans at transcriptional regulatory elements distinct from its site of synthesis to control large-scale transcriptional programmes. N2A cells transfected with a non-targeting control vector were compared to N2A cells transfected with a Paupar knockdown construct. Three biological replicates of each condition were analysed on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

2013-11-21 | E-GEOD-52569 | biostudies-arrayexpress

The long non-coding RNA Paupar regulates the expression of both local and distal genes [Pax6 KD]

Project description:Although some long noncoding RNAs (lncRNAs) have been shown to regulate gene expression in cis, it remains unclear whether lncRNAs can directly regulate transcription in trans by interacting with chromatin genome-wide independently of their sites of synthesis. Here, we describe the genomically local and more distal functions of Paupar, a vertebrate-conserved and central nervous system-expressed lncRNA transcribed from a locus upstream of the gene encoding the Pax6 transcription factor. Knockdown of Paupar disrupts the normal cell cycle profile of neuroblastoma cells and induces neuronal differentiation. Paupar acts in a transcript-dependent manner both locally, to regulate Pax6, as well as distally by binding and regulating genes on multiple chromosomes, in part through physical association with Pax6 protein. Paupar binding sites are enriched near promoters and can function as transcriptional regulatory elements whose activity is modulated by Paupar transcript levels. Our findings demonstrate that a lncRNA can function in trans at transcriptional regulatory elements distinct from its site of synthesis to control large-scale transcriptional programmes. N2A cells transfected with a non-targeting control vector were compared to N2A cells transfected with a Pax6 knockdown construct. Three biological replicates of each condition were analysed on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays.

2013-11-21 | E-GEOD-52568 | biostudies-arrayexpress

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