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| Status |
Public on May 14, 2024 |
| Title |
The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
RNA constitutes a large fraction of chromatin. Spatial distribution and functional relevance of most of RNA interactions within the chromatin remain unknown. We established a landscape analysis of RNA-chromatin interactions in human acute myeloid leukemia (AML). In total more than 50 million interactions were captured in an AML cell line. Protein-coding mRNAs and long non-coding RNAs (lncRNAs) exhibited a substantial number of interactions with chromatin in cis suggesting transcriptional activity. In contrast, small nucleolar RNAs (snoRNAs) and small nuclear RNAs (snRNAs) associated with chromatin predominantly in trans suggesting chromatin specific functions. Of note, snoRNA-chromatin interaction is associated with chromatin modification and is independent of the classical snoRNA-RNP complexes. Two non-canonical C/D box snoRNAs, namely SNORD118 and SNORD3A, displayed high frequency of trans-association with chromatin. The transcription of SNORD118 and SNORD3A was increased upon leukemia transformation and enriched in leukemia stem cells, but decreased during myeloid differentiation. Suppression of SNORD118 and SNORD3A impaired leukemia cell proliferation and colony forming capacity in AML cell lines and in primary AML blast samples. Notably, this effect was leukemia specific with minimal impact on healthy CD34+ hematopoietic stem and progenitor cells (HSPCs). These findings highlight the functional importance of chromatin-associated RNAs overall and in particular of SNORD118 and SNORD3A in maintaining leukemia propagation.
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| Overall design |
Chromatin immunoprecipitation coupled with next generation sequencing (ChIP-seq) for Fibrillarin occupancy on chromatin and histone modifications (including H3K27ac and H3K9me3) in three acute myeloid leukemia cell lines – MV4-11, OCI-AML2 and Kasumi-1, transduced with lentiviral shRNA control or targeting Fibrillarin.
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| Contributor(s) |
Yun H, Rohde C, Müller-Tidow C |
| Citation missing |
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| Submission date |
May 09, 2024 |
| Last update date |
May 15, 2024 |
| Contact name |
Haiyang Yun |
| E-mail(s) |
haiyang.yun@gmail.com
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| Organization name |
Robert Bosch Center for Tumor Diseases
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| Street address |
Auerbachstraße 112
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| City |
Stuttgart |
| ZIP/Postal code |
70376 |
| Country |
Germany |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA1109825 |
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