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| Status |
Public on Jan 31, 2014 |
| Title |
A genome-wide map of transcription start sites specific for acute promyelocytic leukemia reveals deregulation of full-length transcripts |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Transcription start sites are the focal points of transcriptional regulation, where information from regulatory elements is integrated to stabilize initiation of transcription. In humans, most genes have more than one transcription start site, and these often exhibit different tissue specificity, serving as distinct regulatory frameworks for the same gene. Usage of such promoters can also result in differential gene function manifested on the protein level. Alternative promoter usage has been shown to be increased in several disease states, especially cancer. In this study, we have applied the nanoCAGE method to create a genome-wide map of TSS usage in sorted leukemic blasts from acute myeloid leukemia patients, and corresponding normal controls. We show that the nanoCAGE method can replace similar experiments made with microarrays in terms of expression, but also that it uniquely, allow for the identification of alternative promoter usage in cancer cells. We identify 2,162 putative promoters that are significantly differentially regulated between APL and controls. Interestingly, promoters whose usage is upregulated in APL have an increased propensity to be downstream alternative promoters, and conversely, the promoters producing the annotated longest gene variants are commonly downregulated in cancer. We show examples of genes with upregulated downstream promoters, and demonstrate protein domain loss that could contribute to leukemic induction and maintenance. In conclusion, we present the first genome wide promoterome study from rare purified human leukemic cells.
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| Overall design |
nanoCAGE-seq of human acute myeloid leukemia samples vs. normal hematopoietic counterparts, both in replicates
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| Contributor(s) |
Waage JE, Boyd M, Theilgaard KM, Carninci P, Rapin N, Porse BT, Sandelin AG |
| Citation missing |
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| Submission date |
May 01, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Johannes Eichler Waage |
| E-mail(s) |
johannes.waage@bric.ku.dk
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| Phone |
004521232722
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| Organization name |
University Of Copenhagen
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| Department |
Biotech Research and Innovation Center
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| Lab |
Porse / Sandelin
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| Street address |
Ole Maaløesvej 5
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| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA200968 |
| SRA |
SRP022025 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46561_RAW.tar |
10.1 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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