Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Unraveling lineage specific transcription factors involved in the reprogramming of Neuroblastoma from self-renewal to differentiation state

ABSTRACT: Temporal regulation of super enhancer (SE) driven lineage specific transcription factors (TFs), underlies normal developmental programs. Neuroblastoma (NB) arises from an inability of sympathoadrenal progenitors to exit a self-renewal program and terminally differentiate. To identify critical SEs driving TF regulators of NB, we utilized NB cells in which retinoid (RA) induces growth arrest and differentiation. H3K27ac ChIP-seq paired with RNA-seq over a time course of RA treatment revealed that SEs moving in a coordinated manner with four distinct temporal patterns (clusters). SEs that decreased with RA linked to 24 TFs involved in stem cell differentiation (MYCN, GATA3, SOX11). Three other TF SE clusters had sequential waves of activation at 2, 4 and 8 days of RA treatment and involved TFs regulating neural development (GATA2 and SOX4). Our study has identified candidate oncogenic lineage drivers of NB self-renewal and TFs critical for implementing a differentiation program.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147408 | GEO | 2020/07/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

MyoD and FoxO3 mediated hotspot interaction orchestrates super-enhancer activity during myogenic differentiation

Project description:Super-enhancers (SEs) are cis-regulatory elements enriching lineage specific key transcription factors (TFs) to form hotspots. A paucity of identification and functional dissection promoted us to investigate SEs during myoblast differentiation. ChIP-seq analysis of histone marks leads to the uncovering of SEs which remodel progressively during the course of differentiation. Further analyses of TF ChIP-seq enable the definition of SE hotspots co-bound by the master TF, MyoD and other TFs, among which we perform in-depth dissection for MyoD/FoxO3 interaction in driving the hotspots formation and SE activation.

2017-06-02 | GSE93916 | GEO

MyoD and FoxO3 mediated hotspot interaction orchestrates super-enhancer activity during myogenic differentiation (Foxo3 ChIP-seq)

2017-11-01 | GSE99207 | GEO

Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity for Pluripotency and Reprogramming [ChIP-Seq]

Project description:Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for Oct4, Sox2, and Nanog in the enhanceosome assembly and express enhancer RNAs (eRNAs). We sought to dissect the molecular control mechanism of SE activity and eRNA transcription for pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, a key pluripotency and reprogramming factor that guides the ESC-specific enhanceosome assembly and orchestrates the hierarchical transcriptional activation during the final stage of reprogramming, we discovered Tex10 as a novel pluripotency factor that is evolutionally conserved and functionally significant in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation of SEs. Our study sheds new light on epigenetic control of SE activity for cell fate determination. Genome binding/occupancy profiling of Tex10 was performed in mouse embryonic stem cells by ChIP sequencing.

2015-05-07 | E-GEOD-66735 | biostudies-arrayexpress

Selective Disruption of Core Regulatory Transcription [ChIP-seq]

Project description:Activation of identity determining transcription factors (TFs), or core regulatory TFs, is governed by cell-type specific enhancers, an important subset of these being super enhancers (SEs). This mechanism is distinct from constitutive expression of housekeeping genes. The characterization of drug-like small molecules to selectively inhibit core regulatory circuitry is of high interest for treatment of cancers, which are addicted to core regulatory TF function at SEs. Surprisingly, we find histone deacetylases (HDAC) to be an indispensable component of SE-driven transcription. While histone acetylation is a marker for active genes, over accumulation of acetylation selectively halts core regulatory transcription. We show this conundrum may in part be explained by a SE-specific need for resetting histones to maintain SE boundaries, to facilitate enhancer-promoter looping and high levels of transcription.

2019-07-16 | GSE116344 | GEO

Selective Disruption of Core Regulatory Transcription [single cell RNA-seq]

2019-08-27 | GSE121107 | GEO

Selective Disruption of Core Regulatory Transcription [RNA-seq]

2019-05-29 | GSE121106 | GEO

Transcriptome Analysis of Synovial CD14+ cells in Rheumatoid Arthritis Patients

Project description:To understand the pathogenic mechanisms of bone erosion in rheumatoid arthritis (RA), we investigated osteoclast-specific epigenetic programs, RANKL-responsive super-enhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) in human osteoclasts. In this dataset, we sought for functional SE-eRNAs in RA patients' synovial monocytes.

2022-11-01 | GSE203357 | GEO

Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity for Pluripotency and Reprogramming [RNA-Seq]

Project description:Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for Oct4, Sox2, and Nanog in the enhanceosome assembly and express enhancer RNAs (eRNAs). We sought to dissect the molecular control mechanism of SE activity and eRNA transcription for pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, a key pluripotency and reprogramming factor that guides the ESC-specific enhanceosome assembly and orchestrates the hierarchical transcriptional activation during the final stage of reprogramming, we discovered Tex10 as a novel pluripotency factor that is evolutionally conserved and functionally significant in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation of SEs. Our study sheds new light on epigenetic control of SE activity for cell fate determination. RNA sequencing analysis was performed in mouse embryonic stem cells with Luciferase and Tex10 knockdown. RNA-seq Experiments were carry out in two biological replicates.

2015-05-07 | E-GEOD-66734 | biostudies-arrayexpress

Investigation of Genomic RNA Polymerase II-Rich Locations in Osteoclast Precursor Cells

2022-11-01 | GSE203355 | GEO

Chromatin Accessibility Profiling of Osteoclasts Precursor Cells

2022-11-01 | GSE203354 | GEO