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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 29, 2019 |
| Title |
Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation is thought to contribute to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements (TEs). In this study, we used CRISPR/Cas9 technology to delete DNMT1, the key maintenance DNA methyltransferase in human neural progenitor cells (hNPCs). Surprisingly, and in contrast to previous findings in mouse somatic cells, inactivation of DNMT1 in hNPCs resulted in viable proliferating cells despite the global loss of DNA CpG-methylation. DNA demethylation led to specific transcriptional activation and chromatin remodeling of evolutionarily young, hominoid-specific LINE-1 elements (L1s), while older L1s and other classes of TEs remained silent. The activated L1s acted as alternative promoters for many protein-coding genes involved in neuronal functions, revealing a hominoidspecific L1-based transcriptional network controlled by DNA methylation that influences neuronal protein-coding genes. Our results give a novel mechanistic insight into the role of DNA methylation in silencing TEs in somatic human cells, as well as further implicating L1s in human
brain development and disease.
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| Overall design |
CRISPR/Cas9 mediated disruption of DNMT1 in human neural progenitor cells. Guides targeting LacZ as control. Three replicates per condition. 2X125 paired-end RNA-sequencing. 2x150bp WGBS. 1x50bp ChIP-seq.
Please note that the hEmbryo_PE150.hg38*.txt processed data files are associated with the GSM2940637-GSM2940642 samples.
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| Contributor(s) |
Jönsson M, Brattås P, Gustafsson C, Petri R, Yudovich D, Verschuere S, Madsen S, Hansson J, Larsson J, Månsson R, Meissner A, Jakobsson J |
| Citation(s) |
31320637 |
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| Submission date |
Dec 01, 2017 |
| Last update date |
Sep 08, 2019 |
| Contact name |
Per Brattas |
| Organization name |
Lund University
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| Lab |
Clinical Genomics
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| Street address |
Sölvegatan 17
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| City |
Lund |
| ZIP/Postal code |
221 84 |
| Country |
Sweden |
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| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA420729 |
| SRA |
SRP125992 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107580_DNMT1KO.hg38.NCBI.genesBestRefSeq.exon.primary.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
| GSE107580_DNMT1KO.hg38.uniqueMapping.RepeatMasker.notInNCBIexon.txt.filtered.txt.gz |
293.1 Kb |
(ftp)(http) |
TXT |
| GSE107580_DNMT1KO_AF22.hg38.NCBI.genesBestRefSeq.exon.primary.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
| GSE107580_DNMT1KO_AF22.hg38.uniqueMapping.RepeatMasker.notInNCBIexon.txt.filtered.txt.gz |
610.2 Kb |
(ftp)(http) |
TXT |
| GSE107580_RAW.tar |
1.5 Gb |
(http)(custom) |
TAR (of BW, COV) |
| GSE107580_hEmbryo_PE150.hg38.mMap.NCBI.sense.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
| GSE107580_hEmbryo_PE150.hg38.unique.ERE.notInExon.NCBI.ANTISENSE.Srf.txt.gz |
58.9 Mb |
(ftp)(http) |
TXT |
| GSE107580_hEmbryo_PE150.hg38.unique.ERE.notInExon.NCBI.NONstrandSpecific.txt.gz |
59.7 Mb |
(ftp)(http) |
TXT |
| GSE107580_hEmbryo_PE150.hg38.unique.ERE.notInExon.NCBI.sense.txt.gz |
58.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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