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| Status |
Public on Jun 29, 2020 |
| Title |
Oct4-mediated inhibition of Lsd1 activity promotes the active and primed state of pluripotency enhancers [methylRAD-seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Enhancer reactivation and pluripotency gene (PpG) expression could induce stemness and enhance tumorigenicity in cancer stem cells. Silencing of PpG enhancers (PpGe) during embryonic stem cell differentiation involves Lsd1–mediated H3K4me1 demethylation followed by DNA methylation. Here, we observed a widespread retention of H3K4me1 and DNA hypomethylation at PpGe associated with a partial repression of PpGs in F9 embryonal carcinoma cells (ECCs) post-differentiation. The absence of H3K4me1 demethylation could not be rescued by Lsd1 overexpression. Based on the observation that H3K4me1 demethylation is accompanied by strong Oct4 repression in P19 ECCs, we tested if Lsd1-Oct4 interaction affects Lsd1 catalytic activity. Our data show a dose-dependent inhibition of Lsd1 by Oct4 in vitro and retention of H3K4me1 at PpGe post-differentiation in Oct4 overexpressing P19 ECCs. These data suggest that Lsd1-Oct4 interaction in cancer stem cells may establish a primed enhancer state that is susceptible to reactivation leading to aberrant PpG expression.
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| Overall design |
To understand the mechanism by which cancer cells retain PpG expression, we investigated the mechanism of enhancer-mediated regulation of PpG expression in ECCs. This data correspond to genome-wide methylRAD sequencing experiment performed with undifferentiated (UD) and day four (D4) samples. Raw data is provided as FASTQ files. Processed data is provided as BedGraph files and TSV files. TSV files describe all methylated sites and columns are Chr, Sites, CgarType (cigar string – shows match, substitution, etc), count, and type of site (CCGG, CCAGG< or CCTGG).
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| Contributor(s) |
AlAbdi L, Saha D, He M, Dar MS, Utturkar SM, Sudyanti PA, McCune S, H Spears B, Breedlove JA, Lanman NA, Gowher H |
| Citation(s) |
32023463 |
| Submission date |
Aug 01, 2019 |
| Last update date |
Jun 29, 2020 |
| Contact name |
Humaira Gowher |
| E-mail(s) |
hgowher@purdue.edu
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| Organization name |
Purdue University
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| Department |
Department of Biochemistry
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| Street address |
175 South University St.
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| City |
West Lafayette |
| State/province |
IN |
| ZIP/Postal code |
47906 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE135227 |
Oct4-mediated inhibition of Lsd1 activity promotes the active and primed state of pluripotency enhancers |
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| Relations |
| BioProject |
PRJNA558170 |
| SRA |
SRP217158 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE135226_RAW.tar |
111.2 Mb |
(http)(custom) |
TAR (of BEDGRAPH, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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