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The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ChIRP]

ABSTRACT: The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ChIRP]

PROVIDER: PRJNA1109722 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28976253.fastq.gz	Fastqsanger.gz
	SRR28976254.fastq.gz	Fastqsanger.gz
	SRR28976255.fastq.gz	Fastqsanger.gz
	SRR28976256.fastq.gz	Fastqsanger.gz

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The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ChIRP]

Project description: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.

2024-05-14 | GSE267081 | GEO

The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [iMARGI]

Project description:The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [iMARGI]

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The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ChIP-seq]

Project description:The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ChIP-seq]

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The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ATAC-Seq]

Project description:The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ATAC-Seq]

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The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [iMARGI]

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ChIRP-MS of long non-coding RNA HOTAIR

Project description:Accumulating evidence highlights the role of long non-coding RNAs (lncRNA) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, an unbiased and comprehensive method to map its interactome has not yet been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting HOTAIR has functions independent of its (post-)transcriptional mode-of-action.

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The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ATAC-Seq]

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The landscape of RNA-chromatin interaction reveals small non coding RNAs as essential mediators of leukemia maintenance [ChIP-seq]

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Project description:Chromatin-associated long non-coding RNAs (ca-lncRNAs) play important roles in transcriptional regulation. To comprehensively investigate the chromatin interactome of an enhancer-derived ca-lncRNA, LEENE, we performed the Chromatin isolation by RNA purification (ChIRP) to pull down LEENE-associated DNAs, which were subjected to DNA-seq. Specifically, we used 10 previously validated tiling nucleotides targeting different domains based on the predicted secondary structure. LEENE was overexpressed by adenovirus to enhance the ChIRP-seq signals.

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