Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The histone acetylation reader ENL is required for oncogenic transcription driven by super-enhancer and represents a synergistic vulnerability for BET inhibition [ChIP-Seq II]

ABSTRACT: The histone acetylation reader ENL is identifed as a key factor controlling super-enhancer-driven transcription. Therefore, we constructed a targeted degradation system of endogenous ENL protein and investigated the roles of ENL in regulating oncogenic transcription through epigenetic reprogramming.

ORGANISM(S): Homo sapiens

PROVIDER: GSE249553 | GEO | 2024/01/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The histone acetylation reader ENL is required for oncogenic transcription driven by super-enhancer and represents a synergistic vulnerability for BET inhibition [RNA-seq]

Project description:The histone acetylation reader ENL is identifed as a key factor controlling super-enhancer-driven transcription. Therefore, we constructed a targeted degradation system of endogenous ENL protein and investigated the roles of ENL in regulating oncogenic transcription through epigenetic reprogramming.

2024-01-18 | GSE230421 | GEO

The histone acetylation reader ENL is required for oncogenic transcription driven by super-enhancer and represents a synergistic vulnerability for BET inhibition [ChIP-seq]

2024-01-18 | GSE230420 | GEO

The histone acetylation reader ENL is required for oncogenic transcription driven by super-enhancer and represents a synergistic vulnerability for BET inhibition [RNA-Seq II]

Project description:The histone acetylation reader ENL is identifed as a key factor controlling super-enhancer-driven transcription. We thus perturbed BRD4, a well-known super-enhancer regulator, protein expression with a well-validated BRD4 PROTAC (proteolysis targeting chimeric) compound dBET1 and examined whether BRD4 was required for proper function of ENL in regulation gene transcription.

2024-01-18 | GSE249552 | GEO

The histone acetylation reader ENL is required for oncogenic transcription driven by super-enhancer and represents a synergistic vulnerability for BET inhibition

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

2024-01-17 | GSE230422 | GEO

ENL Links Histone Acetylation to Oncogenic Gene Expression in AML

Project description:Cancer cells are characterized by aberrant epigenetic landscapes and often exploit the chromatin machinery to activate oncogenic gene expression programs1. The recognition of modified histones by “reader” proteins constitutes a key mechanism underlying these processes; therefore targeting such pathways holds clinical promise, as exemplified by the recent development of BET bromodomain inhibitors2,3. We recently identified the YEATS domain as a novel acetyllysine-binding module4, yet its functional importance in human cancer remains unknown. Here we show that the YEATS domain-containing protein ENL, but not its paralog AF9, is required for disease maintenance in a variety of acute myeloid leukaemias (AML). CRISPR-Cas9 mediated depletion of ENL led to anti-leukemic effects, including increased terminal myeloid differentiation and suppression of leukaemia growth in vitro and in vivo. Biochemical and crystal structural studies in vitro and ChIP-seq analyses in leukaemia cells revealed that ENL binds to acetylated histone H3, and colocalizes with H3K27ac and H3K9ac on the promoters of actively transcribed genes that are essential for leukaemias. Disrupting the interaction between the YEATS domain and histone acetylation via structure-based mutagenesis reduced RNA polymerase II recruitment on ENL target genes, thus leading to suppression of oncogenic gene expression programs. Importantly, disruption of ENL’s functionality further sensitized leukaemia cells to BET inhibitors. Together, our study identifies ENL as a histone acetylation reader that regulates oncogenic transcriptional programs in AML and suggests that displacement of ENL from chromatin is a promising epigenetic therapy alone or in combination with BET inhibitors for AML

2017-02-23 | GSE80779 | GEO

ENL Links Histone Acetylation to Oncogenic Gene Expression in AML

2017-04-05 | GSE80774 | 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

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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