Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE243866 | GEO | 2024/05/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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.

2024-05-27 | GSE243867 | 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: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 (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

Small-molecule inhibition of the acyl-lysine reader ENL as a strategy against acute myeloid leukemia [ChIP-Seq]

Project description:Acute myeloid leukemia (AML) is characterized by dysregulated transcriptional programs and these programs require support from chromatin regulators to maintain their hyperactive state. Recent studies have identified the histone acylation ‘reader’ ENL as being a critical dependency in AML, but the potential of therapeutic applications targeting this chromatin reader remains poorly understood. Here, we present a potent and orally bioavailable small-molecule inhibitor of ENL, TDI-055, which displaces ENL from chromatin by competitively blocking the interaction of its YEATS domain with acylated histones. We show that TDI-055 treatment preferentially inhibited the proliferation of human leukemia cells harboring MLL translocations or NPM1 mutations. Through a CRISPR/Cas9 saturated mutagenesis screen, we uncovered an ENL mutant that could confer cells resistance to TDI-055, thus providing compelling proof for the on-target activity of the compound. Rapid displacement of ENL from chromatin resulted in decreased recruitment of select ENL-associated complexes and impaired RNA polymerase II elongation which, in turn, led to the suppression of critical leukemogenic gene expression programs. Finally, pharmacological inhibition of ENL in vivo led to reduced AML growth and prolonged survival in cell line and patient-derived xenograft (PDX) models. Collectively, these results provide critical evidence and mechanistic insights to establish inhibition of ENL as a potential therapeutic strategy against molecularly defined AML, laying the foundation for rapid clinical translation of this approach.

2022-10-05 | GSE185093 | GEO

Small-molecule inhibition of the acyl-lysine reader ENL as a strategy against acute myeloid leukemia [RNA-Seq]

2022-10-05 | GSE185091 | GEO

Condensate-promoting ENL mutation induces tumorigenesis via chromatin remodeling [RNA-seq]

Project description:Gain-of-function mutations in the chromatin ‘reader’ ENL, identified in AML and Wilms tumor, have been shown to induce aberrant formation of transcriptional condensates in cellular systems. However, the precise role of these mutations and their condensate forming property in tumorigenesis remains unclear. By creating a conditional knock-in mouse model for the most prevalent ENL mutation, we establish ENL mutant as a bona fide oncogenic driver of acute myeloid leukemia in vivo. Heterozygous expression of ENL mutant perturbs the normal hematopoietic hierarchy and results in the aberrant expansion of myeloid progenitors with increased self-renewal property. Furthermore, the ENL mutant remodels histone modifications to alter differentiation processes and drive oncogenic gene expression during hematopoietic development. Importantly, targeted point mutagenesis to disrupt the condensate formation property completely abolishes ENL mutant’s oncogenic function in hematopoietic stem and progenitor cells (HSPCs). Lastly, short-term treatment with a small molecule inhibitor that blocks the acetyl-binding activity of ENL mutant reverts its impact on chromatin and significantly delays leukemia development in mice. Our studies reveal the crucial biological function of mutation-induced transcriptional condensates in chromatin regulation and cancer in vivo and provide proof-of-concept for targeting of pathogenic condensates as a promising therapy for certain cancers.

2024-04-14 | GSE239469 | GEO

Condensate-promoting ENL mutation induces tumorigenesis via chromatin remodeling [ChIP-seq and CUT&Tag]

2024-04-14 | GSE239468 | GEO

ENL reads histone β-hydroxybutyrylation to modulate gene transcription (RNA-Seq)

Project description:Histone modifications are typically recognized by chromatin-binding protein modules (referred to as “readers”) to mediate fundamental processes such as transcription. Lysine β-hydroxybutyrylation (Kbhb) is a new type of histone mark that couples metabolism to gene expression. However, the readers that prefer histone Kbhb remain elusive. This knowledge gap must be filled in order to reveal the molecular mechanism of this epigenetic regulation. Herein, we developed a chemical proteomic approach, relying upon multivalent photoaffinity probes to capture binders of the mark and identified ENL as a novel target of H3K9bhb. Biochemical studies and CUT&Tag analysis further suggested that ENL favorably binds to H3K9bhb, and co-localizes with it on promoter regions to modulate gene expression. Notably, disrupting the interaction between H3K9bhb and ENL via structure-based mutation leads to the suppressed expression of the gene like MYC that drives cell proliferation.

2024-05-06 | GSE266269 | GEO

ENL reads histone β-hydroxybutyrylation to modulate gene transcription (CUT&Tag)

2024-05-06 | GSE266268 | GEO

Transcriptomic profiling of MLL-ENL and delta YEATS mutant

Project description:To investigate the contribution of ENL YEATS domain and downstream sequences in MLL-ENL leukemogenesis program, we generated MLL-ENL and MLL-ENL ∆YEATS (ENL aa372-559) cell lines by retrovirally introducing these constructs into lineage negative hematopoietic stem and progenitor cells (HSPCs).

2023-02-27 | GSE211523 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data