Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BCL6 confers KRAS-mutant NSCLCs resistance to BET inhibitors [ChIP-Seq]

ABSTRACT: We report that BCL6 interacts with BRD3 and that BRD3 inhibition upregulates BCL6. By obtaining sequence from chromatin immunoprecipitated DNA of A549 cells, we generated genome-wide binding gene spectrums of BCL6 and BRD3. By locating -3000 to +200 bps around TSS, we find that BRD3 binds to the promoters of 2470 genes and that BCL6 binds to the promoters of 694 genes, with 82 genes shared by BRD3 and BCL6. Interestingly, BCL6 itself is one of these 82 shared genes, implying that BCL6 mediated self-repression may require the participation of BRD3. Other shared genes includes SGK2, IDH2, HOXB6, SIRT1, SOCS3 and ZFNs, demonstrating the widely involvement of BRD3 in the regulatory role of BCL6. To examine the dependency of BCL6 on BRD3, we also compared BCL6-binding spectrums with or without a BET inhibitor, OTX015. The ChIP-seq data with BCL6 antibody exhibited a diverse BCL-binding spectrum composed of 731 genes in OTX015 treatment, with only 117 genes overlapped with that of DMSO treatment. These data demonstrates that BET inhibition is sufficient to change BCL6-binding spectrum. This study provides a new insight of BCL6 regulatory roles in KRAS-mutant NSCLCs, where BRD3 is recruited by BCL6 and affect BCL6 binding preference as a cofactor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE119863 | GEO | 2018/09/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

BCL6 confers KRAS-mutant NSCLCs resistance to BET inhibitors

Project description:We report that OTX015 upregulates BCL6 in KRAS-mutant NSCLC cells. Considering that both BCL6 and BET proteins regulate target genes by affecting transcription, we performed an RNA-seq experiment to identify downstream genes which response to OTX015. Retinal mRNA profiles of A549 cells treated with DMSO (0.1% for 6 hr) and OTX015 (1 μM for 6 hr) were generated by deep sequencing, in triplicate, using the SOLiD v4 sequencing platform. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows-Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT-PCR validation was performed using TaqMan and SYBR Green assays.

2019-08-15 | GSE118645 | GEO

Functions of BET proteins in GATA1-mediated transcription [ChIP-seq]

Project description:Transcription factor GATA1 binding in erythroblasts in the presence and absence of BET inhibitor JQ1, and BET protein BRD3 and BRD4 binding in erythroblasts in the presence and absence of GATA1. Inhibitors of Bromodomain and Extra-Terminal motif proteins (BETs) are being evaluated for the treatment of cancer and other diseases yet their physiologic mechanisms remain largely unknown. We used genomic and genetic approaches to examine BET function in a hematopoietic maturation system driven by GATA1, an acetylated transcription factor previously shown to interact with BETs. We found that while BRD3 occupied the majority of GATA1 binding sites, BRD2 and BRD4 were also recruited to a subset of GATA1-occupied sites. Functionally, BET inhibition impaired GATA1-mediated transcriptional activation, but not repression, genome-wide. Co-activation by BETs was accomplished both by facilitating genomic occupancy of GATA1 and subsequently supporting transcription activation. Using a combination of CRISPR/CAS9-mediated genomic engineering and shRNA approaches we observed that depletion of either BRD2 or BRD4 alone blunted erythroid gene activation, while depletion of BRD3 only affected erythroid transcription in the setting of BRD2 deficiency. These results suggest that pharmacologic BET inhibition should be interpreted in the context of distinct steps in transcriptional activation and partially overlapping functions among BET family members. GATA1 null erythroblasts (G1E) conditionally expressing GATA1 as a GATA1-ER fusion protein were induced to express GATA1 by addition of 100nM estradiol for 24 hours. For GATA1 binding experiments this occurred in the absence or presence of 250nM JQ1. For BRD3 and BRD4 occupancy experiments G1E cells were compared to G1E cells with activated GATA1-ER fusion protein.

2015-02-23 | E-GEOD-62736 | biostudies-arrayexpress

Decoding the gene promoters binding with BRD3 in LPS-primed THP1 monocytes

Project description:To screen the genes regulated by BRD3 in the THP1 monocytes induced by LPS, THP1 monocytes were treated by LPS for 1 hour in the presence or absence of OTX015

2023-12-31 | GSE234162 | GEO

ChIP-seq for E4BP4 in CD4+ T cell

Project description:Here, using ChIP-seq, we demonstrate that the transcriptional repressor Adenovirus E4 promoter-binding protein (E4BP4) binds directly to the Bcl6 promoter, which a key transcription factor controlling Tfh cell differentiation. By obtaining sequence from chromatin immunoprecipitated DNA of E4BP4 overexpressing CD4+T cells, we generated genome-wide binding gene spectrums of E4BP4. These results reveal that E4BP4 interacts with BCL6 and E4BP4 directly modulated the expression of Bcl6 to reveal the mechanism downstream of E4BP4 that regulates Tfh cell differentiation.

2021-01-19 | GSE121387 | GEO

Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma (ChIP-Seq)

Project description:Purpose: Identification of core transcriptional regulatory programs and bromodomain and extraterminal (BET) protein dependency in liposarcoma (LPS) Methods: ChIP-seq and RNA-seq were performed on LPS cells. Antibodies against H3K27ac, H3K4me1, H3K4me3, RNA-Pol2, BRD2, BRD3, BRD4, FOSL2, pan-RUNX, and DDIT3 (FUS-DDIT3) were used for ChIP-seq assays. The transcriptome responses of LPS141 and MLS402 cells to OTX015 and ARV-825 were compared. Result: We generated genome-wide chromatin-state maps of LPS cells. By charting the super-enhancer structures, we identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. This study also provides a framework for discovering and targeting of core oncogenic transcriptional programs.

2019-04-01 | GSE111253 | GEO

Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma (RNA-Seq)

2019-04-01 | GSE111252 | GEO

BRD3 regulates the inflammatory and stress response in rheu-matoid arthritis synovial fibroblasts

Project description:Individual functions of members of the bromodomain (BRD) and extra-terminal (BET) protein family underlying the anti-inflammatory effects of BET inhibitors in rheumatoid arthritis (RA) are incompletely understood. Here we aimed to analyze regulatory functions of BRD3, an under-studied member of the BET protein family, in RA synovial fibroblasts (FLS). BRD3 was silenced in FLS prior to stimulation with TNF. Alternatively, FLS were treated with I-BET. Transcriptomes were analyzed by RNA sequencing (RNAseq), followed by pathway enrichment analysis. We confirmed results for selective target genes by Real-time PCR, ELISA and Western blotting. BRD3 regulates the expression of several cytokines and chemokines in FLS, and positively correlates with inflammatory scores in the RA synovium. In addition, RNAseq pointed to a profound role of BRD3 in regulating FLS proliferation, metabolic adaption, and response to stress, including oxidative stress, and autophagy. BRD3 acts as an upstream regu-latory factor that integrates the response to inflammatory stimuli and stress conditions in FLS and executes many functions of BET proteins that have previously identified using pan-BET inhibitors.

2023-11-30 | GSE247226 | GEO

Control of embryonic stem cell identity by BRD4-dependent transcriptional elongation of super-enhancer associated pluripotency genes

Project description:BET-regulated transcriptome and BRD4, BRD2, BRD3 and Pol II ChIP-seq datasets in human ESCs before and after BET inhibition. Transcription factors and chromatin remodeling complexes are key determinants of embryonic stem cell (ESC) identity. In this study, we investigate the role of BRD4, a member of the bromodomain and extra-terminal domain (BET) family of epigenetic reader proteins, in control of ESC identity. We performed RNA-seq analyiss in the presense of small molecule inhibitors of BET proteins to show that BRD4 positively regulates the ESC transcriptome. We also integrated RNA-seq analysis with ChIP-sequencing datasets s for BRD4 (and for other BRD2 and BRD3) to demonstrate that BRD4 binds SEs and regulates the expression of SE-associated pluripotency genes. We have also conducted ChIP-seq analysis for Pol II binding to demonstrate that SE-associated genes depend on BRD4-dependent Pol II binding at TSS and gene body for their productive transcriptional elongation.

2014-09-26 | GSE60171 | GEO

Functions of BET proteins in GATA1-mediated transcription [ChIP-seq]

2015-02-23 | GSE62736 | GEO

RNA-seq of human pancreatic cancer cell line SUIT-2 infected with an adenoviral construct and treated with epigenetic modifiers compared to uninfected and untreated controls

Project description:Transcriptional profiling of the human pancreatic cancer cell line SUIT-2 that were infected with a GFP encoding adenoviral construct based on Human Adenovirus 5 and treated with epigenetic modifiers I-bet-762, NEO27034 or OTX015 compared to uninfected and untreated cells. Cells were infected with 1pfu AdWTGFP in serum free media for 2 hours. Cells were then washed and cultured in media containing 2% FBS for 10 hours. Cells were then treated with I-bet-762, NEO27034, OTX015 or DMSO in media containing 2% FBS for 12 hours. Infected GFP+ cells were isolated by FACS. GFP+ and control cells were processed for RNA-seq.

2024-02-14 | E-MTAB-13108 | biostudies-arrayexpress

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