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Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci

ABSTRACT: Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci

PROVIDER: PRJNA722507 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14255100_1.fastq.gz	Fastqsanger.gz
	SRR14255100_2.fastq.gz	Fastqsanger.gz
	SRR14255101_1.fastq.gz	Fastqsanger.gz
	SRR14255101_2.fastq.gz	Fastqsanger.gz
	SRR14255102_1.fastq.gz	Fastqsanger.gz

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Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [RNA-Seq]

Project description:The noncoding genome presents a largely untapped source of new biological insights, including thousands of long noncoding RNA (lncRNA) loci. While some produce bona fide functional transcripts, others exert transcript-independent regulatory effects, and the lack of predictive features renders mechanistic dissection a major challenge. Here, we describe MYNRL15: a noncoding regulatory locus on chromosome 15 and pan-myeloid leukemia dependency identified by a CRISPR screen of lncRNA signatures from hematopoietic stem and progenitor cells (HSPCs) and acute myeloid leukemia (AML) samples We demonstrate that the loss of cis-regulatory DNA elements in the locus, rather than its transcriptional products, drives its perturbation phenotype, triggering a global downregulation of oncogenic pathways, coordinated dysregulation of chromosome 15 neighborhoods, and formation of a tumor-suppressive, long-range chromatin interaction with the base of a distal loop. In addition, MYNRL15 perturbation selectively impaired primary AML blasts over normal HSPCs in vitro, and depleted patient-derived xenografts in vivo, providing evidence for oncogenic vulnerabilities at chromatin-regulating, noncoding loci. MYNRL15 is characterized by elevated CTCF binding, low expression, and short span - features shared by hundreds of lncRNA genes, nearly half of which associate with clinical aspects in AML patient cohorts. We propose these as a new class of functional genetic elements carrying both therapeutic potential for AML and profound implications for cancer pathophysiology in general, as exemplified by MYNRL15.

2023-10-04 | GSE172238 | GEO

Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [ATAC-Seq]

2023-10-04 | GSE172235 | GEO

Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [capture-C]

Project description:he noncoding genome presents a largely untapped source of new biological insights, including thousands of long noncoding RNA (lncRNA) loci. While some produce bona fide functional transcripts, others exert transcript-independent regulatory effects, and the lack of predictive features renders mechanistic dissection a major challenge. Here, we describe MYNRL15: a noncoding regulatory locus on chromosome 15 and pan-myeloid leukemia dependency identified by a CRISPR screen of lncRNA signatures from hematopoietic stem and progenitor cells (HSPCs) and acute myeloid leukemia (AML) samples We demonstrate that the loss of cis-regulatory DNA elements in the locus, rather than its transcriptional products, drives its perturbation phenotype, triggering a global downregulation of oncogenic pathways, coordinated dysregulation of chromosome 15 neighborhoods, and formation of a tumor-suppressive, long-range chromatin interaction with the base of a distal loop. In addition, MYNRL15 perturbation selectively impaired primary AML blasts over normal HSPCs in vitro, and depleted patient-derived xenografts in vivo, providing evidence for oncogenic vulnerabilities at chromatin-regulating, noncoding loci. MYNRL15 is characterized by elevated CTCF binding, low expression, and short span - features shared by hundreds of lncRNA genes, nearly half of which associate with clinical aspects in AML patient cohorts. We propose these as a new class of functional genetic elements carrying both therapeutic potential for AML and profound implications for cancer pathophysiology in general, as exemplified by MYNRL15.

2023-10-04 | GSE172237 | GEO

Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [CUT&RUN]

2023-10-04 | GSE172236 | GEO

Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [capture-C]

Project description:Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [capture-C]

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Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [RNA-Seq]

Project description:Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [RNA-Seq]

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Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [CUT&RUN]

Project description:Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [CUT&RUN]

| PRJNA722505 | ENA

Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [ATAC-Seq]

Project description:Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci [ATAC-Seq]

| PRJNA722506 | ENA

Myeloid leukemia dependency MYNRL15 exemplifies class of CTCF-bound lncRNA loci

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-04 | GSE172240 | GEO

RNA helicase DHX15 exemplifies a unique dependency in acute leukemia

Project description:RNA helicase DHX15 exemplifies a unique dependency in acute leukemia

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