The role of Erg in B cell development (ChIP-Seq)
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ABSTRACT:
PROVIDER: PRJNA549273 | ENA |
REPOSITORIES: ENA
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Project description:The role of Erg in B cell development (ATAC-Seq)
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Project description:ChIP-seq of B-cell progenitors and Rag1CreT/+;ErgΔ/Δ thymocytes for Erg transcription factor
2020-04-14 | GSE132853 | GEO
Project description:Transcription factors play a key role in the development of a number of cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the ETS transcription factor ERG is recurrently rearranged and likely plays a critical role in prostate oncogenesis. Here we identified a series of peptides from a phage-display library that interact specifically with the DNA binding domain of ERG. The interactive interface was mapped to 9-residues in the 3rd helix of the ETS domain that is critical for ERG transcriptional activity. The peptides were found to efficiently disrupt ERG-mediated protein-protein interactions, transcription, DNA damage, and cell invasion, as well as attenuate ERG recruitment to target gene loci. Furthermore, a retroinverso peptidomimetic version of the peptide sequence suppressed tumor growth, intravasation, and metastasis in vivo. Taken together, our results demonstrate that transcription factors have specific residues important for protein-protein interactions and disrupting those critical interactions may be an effective therapeutic strategy. Examination of ERG in VCaP cells with respect to peptidomimetics treatment
2014-07-15 | E-GEOD-58939 | biostudies-arrayexpress
Project description:Transcription factors play a key role in the development of a number of cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the ETS transcription factor ERG is recurrently rearranged and likely plays a critical role in prostate oncogenesis. Here we identified a series of peptides from a phage-display library that interact specifically with the DNA binding domain of ERG. The interactive interface was mapped to 9-residues in the 3rd helix of the ETS domain that is critical for ERG transcriptional activity. The peptides were found to efficiently disrupt ERG-mediated protein-protein interactions, transcription, DNA damage, and cell invasion, as well as attenuate ERG recruitment to target gene loci. Furthermore, a retroinverso peptidomimetic version of the peptide sequence suppressed tumor growth, intravasation, and metastasis in vivo. Taken together, our results demonstrate that transcription factors have specific residues important for protein-protein interactions and disrupting those critical interactions may be an effective therapeutic strategy.
2014-07-15 | GSE58939 | GEO
Project description:The transcription factor ERG regulates super-enhancers in endothelial cells [ERG ChIP-seq]
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Project description:B-cell development is dependent on the coordinated expression and cooperation of several transcription factors. Here, we show that the transcription factor ETS Related Gene (ERG) is crucial for normal B-cell development, and that its deletion results in a substantial loss of bone marrow B-cell progenitors and peripheral B-cells as well as a skewing of splenic B-cell populations. We found that ERG-deficient B-lineage cells exhibited an early developmental block, at the pre-B cell stage, and proliferated less. The cells failed to express the immunoglobulin heavy chain due to inefficient V-to-DJ recombination and cells that managed to undergo recombination displayed a strong bias against incorporation of distal V gene segments. Furthermore, antisense transcription at PAX5-activated intergenic repeat (PAIR) elements located in the distal region of the Igh locus was completely dependent on ERG. These findings identify ERG as a novel critical regulator of B-cell development by ensuring efficient and balanced V-to-DJ recombination.
2019-11-24 | GSE128977 | GEO
Project description:B-cell development is dependent on the coordinated expression and cooperation of several transcription factors. Here, we show that the transcription factor ETS Related Gene (ERG) is crucial for normal B-cell development, and that its deletion results in a substantial loss of bone marrow B-cell progenitors and peripheral B-cells as well as a skewing of splenic B-cell populations. We found that ERG-deficient B-lineage cells exhibited an early developmental block, at the pre-B cell stage, and proliferated less. The cells failed to express the immunoglobulin heavy chain due to inefficient V-to-DJ recombination and cells that managed to undergo recombination displayed a strong bias against incorporation of distal V gene segments. Furthermore, antisense transcription at PAX5-activated intergenic repeat (PAIR) elements located in the distal region of the Igh locus was completely dependent on ERG. These findings identify ERG as a novel critical regulator of B-cell development by ensuring efficient and balanced V-to-DJ recombination.
2019-11-24 | GSE128975 | GEO
Project description:ERG is a transcriptional factor, which is recombined with promoter of TMPRSS2 and prominently overexpressed in half of human prostate cancers. The mechanisms of ERG-mediated oncogenesis are not completely understood. We performed an unbiased Mass Spectrometry screen for ERG-binding proteins and found that ERG binds to MTDH/SND1 protein complex in prostate cancer cells. We determined that ERG binds to the SND1/MTDH protein complex via SND1 and this interaction plays a critical role in ERG-mediated cancer.
2023-03-22 | PXD036882 | Pride
Project description:Transcription factors play a key role in the development of diverse cancers, and therapeutically targeting them has remained a challenge. In prostate cancer, the gene encoding the transcription factor ERG is recurrently rearranged and plays a critical role in prostate oncogenesis. Here, we identified a series of peptides that interact specifically with the DNA binding domain of ERG. The most prevalent consensus peptide series matched the tumor suppressor Deleted in Liver Cancer 1 (DLC1). ERG inhibitory peptides and derived peptidomimetics (EIPs) bound with high affinity and specificity leading to proteolytic degradation of ERG. The EIPs attenuated ERG-mediated transcription, chromatin recruitment, protein-protein interactions, cell invasion, and tumor growth. Thus, peptidomimetic targeting of transcription factor fusion products may provide a promising therapeutic strategy for prostate cancer as well as other cancers.
2014-07-15 | GSE58940 | GEO