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Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney

ABSTRACT: Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney

PROVIDER: PRJNA1020190 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26151721.fastq.gz	Fastqsanger.gz
	SRR26151722.fastq.gz	Fastqsanger.gz
	SRR26151723.fastq.gz	Fastqsanger.gz
	SRR26152456_1.fastq.gz	Fastqsanger.gz
	SRR26152456_2.fastq.gz	Fastqsanger.gz

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Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (scRNA-Seq)

Project description:ENL is an epigenetic acetylation reader and represents the most frequently mutated epigenetic regulator in Wilms tumor. In this study, we established an in vivo mouse model with the ENL hotspot mutation Enl-T1. We performed single-cell RNA sequencing (scRNA-seq) analysis for the Enl-WT and T1 embryonic kidney to study the transcriptional mechanism underlying the kidney developing defeat induced by the Enl mutation.

2024-05-27 | GSE243870 | GEO

Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (RNA-Seq)

Project description:ENL is an epigenetic acetylation reader and represents the most frequently mutated epigenetic regulator in Wilms tumor. In this study, we established an in vivo mouse model with the ENL hotspot mutation Enl-T1. Here we performed RNA sequencing (RNA-seq) analysis for human embryonuc kidney cell line HEK293 with ENL-WT, T1 or T2 to study the transcriptional changes induced by ENL mutations and whether those alterations can be rescued by treating the cells with the specific ENL inhibitor TDI-11055.

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Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (ChIP-Seq)

Project description:ENL is an epigenetic acetylation reader and represents the most frequently mutated epigenetic regulator in Wilms tumor. In this study, we established an in vivo mouse model with the ENL hotspot mutation Enl-T1. Here we performed ChIP sequencing (ChIP-seq) analysis for human embryonuc kidney cell line HEK293 with ENL-WT or T1 to study the genomic binding site alterations induced by ENL mutation and whether those alterations can be rescued by treating the cells with the specific ENL inhibitor TDI-11055.

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Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (snATAC-Seq)

Project description:ENL is an epigenetic acetylation reader and represents the most frequently mutated epigenetic regulator in Wilms tumor. In this study, we established an in vivo mouse model with the ENL hotspot mutation Enl-T1. We performed single-nuclei ATAC sequencing (snATAC-seq) analysis for the Enl-WT and T1 embryonic kidney to study the open chromatin dynamics and gene regulatory mechanism underlying the kidney developing defeat induced by the Enl mutation.

2024-05-27 | GSE243868 | GEO

Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (scRNA-Seq)

Project description:Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (scRNA-Seq)

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Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (RNA-Seq)

Project description:Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (RNA-Seq)

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Project description:Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (snATAC-Seq)

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Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (ChIP-Seq)

Project description:Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney (ChIP-Seq)

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Wilms tumor-associated ENL mutants promote MOZ/MORF-mediated DOT1L loading in kidney tumor and leukemia

Project description:ENL is mutated in both Wilms tumor and leukemia which are the two major types of childhood cancers that occur at an early age. This study demonstrates that ENL mutants promote the loading of the DOT1L complex onto promoters in a MOZ/MORF histone acetyltransferase- dependent manner. The ENL protein is an epigenetic hub that interacts with multiple functionally distinct protein complexes to regulate transcription. MOZ binds to ENL through its YEATS domain to form a MOZ/ENL complex, which further recruits a DOT1L/AF10 complex and loads the ENL/DOT1L/AF10 complex onto nearby chromatin. Small indels in the YEATS domain increase the affinity to MOZ/MORF, which potentiates the interaction with ENL and the loading of the DOT1L complex, thereby hyperactivating HOX gene expression in embryonic kidney cells and hematopoietic cells. This oncogenic transformation can be suppressed by inhibitors of the histone-modifying activities of MOZ/MORF and DOT1L, paving the way for molecular targeted therapies against ENL-mutated cancers.

2025-07-05 | PXD053676 | JPOST Repository

Single-Cell multi-omics reveals disrupted gene regulatory landscape and cell differentiation by Wilms tumor-associated ENL mutation in the developing kidney

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

2024-05-27 | GSE243871 | GEO