Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA309980 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Targeting CREBBP/EP300 bromodomains in cancer
| PRJNA433209 | ENA
Project description:C4-2B prostate cancer cells were transfected with siRNA against a non-specific (NS) sequence, siRNA specifically targeting EP300, or siRNA specifically targeting CREBBP. We tested the hypothesis that their exists different subgroups of genes that are preferentially affected by p300 or CBP depletion. Cells were treated with 10nM dihydrotestosterone (DHT) for 16 hours and total RNA was extracted to check for changes in gene expression.
2011-12-15 | E-GEOD-31873 | biostudies-arrayexpress
Project description:We found that the bone marrow microenvironment of Crebbp+/- mice was unable to properly maintain the immature stem - and progenitor pools. Instead, it stimulates myeloid differentiation that progresses into a myeloproliferative-like disease. Since CREBBP is a transcriptional co-activator, we used gene expression analysis to globally assess functional deficiencies in Crebbp+/- bone marrow stroma cells at a molecular level. Ep300 encodes a protein which is highly similar in structure and function to CREBBP; nevertheless, Ep300+/- mice suffer neither excessive myeloid differentiation nor loss of HSCs. Therefore, to identify expression changes specifically related to Crebbp heterozygosity, we focused on genes that showed significant differences in expression levels between Crebbp+/- and wild-type bone marrow stroma but no difference between Ep300+/- and wild-type. Bone marrow stroma was established from wild-type, Crebbp+/- and Ep300+/- mice that were 3-4 months old for RNA extraction and hybridization on Affymetrix microarrays. There are 4 biological replicates for each genotype used.
2011-03-01 | E-GEOD-24773 | biostudies-arrayexpress
Project description:C4-2B prostate cancer cells were transfected with siRNA against a non-specific (NS) sequence, siRNA specifically targeting EP300, or siRNA specifically targeting CREBBP. We tested the hypothesis that their exists different subgroups of genes that are preferentially affected by p300 or CBP depletion.
2011-12-15 | GSE31873 | GEO
Project description:Changes in gene expression caused by CREBBP/EP300 bromodomain inhibitors in breast cancer cell lines
2021-05-18 | GSE114937 | GEO
Project description:Early placenta development involves cytotrophoblast differentiation into extravillous trophoblast (EVT) and syncytiotrophoblast (STB). Defective trophoblast development and function may result in severe pregnancy complications, including fetal growth restriction and pre-eclampsia. The incidence of these complications is increased in pregnancies of fetuses affected by Rubinstein–Taybi syndrome, a developmental disorder predominantly caused by heterozygous mutations in CREB-binding protein (CREBBP) or E1A-binding protein p300 (EP300). Although the acetyltransferases CREBBP and EP300 are paralogs with many overlapping functions, the increased incidence of pregnancy complications is specific for EP300 mutations. We hypothesized that these complications have their origin in early placentation and that EP300 is involved in that process. Therefore, we investigated the role of EP300 and CREBBP in trophoblast differentiation, using human trophoblast stem cells (TSCs) and trophoblast organoids. We found that pharmacological CREBBP/EP300 inhibition blocks differentiation of TSCs into both EVT and STB lineages, and results in an expansion of TSC-like cells under differentiation-inducing conditions. Specific targeting by RNA interference or CRISPR/Cas9-mediated mutagenesis demonstrated that knockdown of EP300 but not CREBBP, inhibits trophoblast differentiation, consistent with the complications seen in Rubinstein–Taybi syndrome pregnancies. By transcriptome sequencing, we identified transforming growth factor alpha (TGFA, encoding TGF-α) as being strongly upregulated upon EP300 knockdown. Moreover, supplementing differentiation medium with TGF-α, which is a ligand for the epidermal growth factor receptor (EGFR), likewise affected trophoblast differentiation and resulted in increased TSC-like cell proliferation. These findings suggest that EP300 facilitates trophoblast differentiation by interfering with at least EGFR signaling, pointing towards a crucial role for EP300 in early human placentation.
2023-12-19 | GSE250424 | GEO
Project description:We found that the bone marrow microenvironment of Crebbp+/- mice was unable to properly maintain the immature stem - and progenitor pools. Instead, it stimulates myeloid differentiation that progresses into a myeloproliferative-like disease. Since CREBBP is a transcriptional co-activator, we used gene expression analysis to globally assess functional deficiencies in Crebbp+/- bone marrow stroma cells at a molecular level. Ep300 encodes a protein which is highly similar in structure and function to CREBBP; nevertheless, Ep300+/- mice suffer neither excessive myeloid differentiation nor loss of HSCs. Therefore, to identify expression changes specifically related to Crebbp heterozygosity, we focused on genes that showed significant differences in expression levels between Crebbp+/- and wild-type bone marrow stroma but no difference between Ep300+/- and wild-type.
2011-03-01 | GSE24773 | GEO
Project description:Inactivating mutations of the CREBBP acetyltransferase and, at lower frequencies, its paralogue EP300 are among the most common genetic alterations in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most frequent B cell malignancies. Here we uncover unexpected distinct functions for CREBBP and EP300 in the germinal center (GC), i.e. the target structure for most human B cell lymphomas. We show that these proteins modulate non-overlapping transcriptional programs that are preferentially enriched in biological functions associated with the separate anatomic compartments of the GC. Consistently, deletion of CREBBP or EP300 have opposing effects on GC formation in vivo. Nonetheless, these proteins partially compensate for each other to maintain a minimal threshold of acetyltransferase activity and guarantee homeostatic control of the GC, which is completely abrogated by their combined loss. This synthetic lethal interaction is retained in DLBCL cells, identifying an Achille’s heel in CREBBP-mutant lymphomas that could be pharmacologically targeted by using a novel, selective small molecule inhibitor of the CREBBP/EP300 bromodomain. These data shed light on the unique roles of CREBBP and EP300 in the physiology and pathology of GC B cells, and provide a proof-of-principle for the development and testing of EP300 inhibition as a therapeutic strategy in these diseases.
2021-06-01 | GSE124192 | GEO
Project description:Inactivating mutations of the CREBBP acetyltransferase and, at lower frequencies, its paralogue EP300 are among the most common genetic alterations in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most frequent B cell malignancies. Here we uncover unexpected distinct functions for CREBBP and EP300 in the germinal center (GC), i.e. the target structure for most human B cell lymphomas. We show that these proteins modulate non-overlapping transcriptional programs that are preferentially enriched in biological functions associated with the separate anatomic compartments of the GC. Consistently, deletion of CREBBP or EP300 have opposing effects on GC formation in vivo. Nonetheless, these proteins partially compensate for each other to maintain a minimal threshold of acetyltransferase activity and guarantee homeostatic control of the GC, which is completely abrogated by their combined loss. This synthetic lethal interaction is retained in DLBCL cells, identifying an Achille’s heel in CREBBP-mutant lymphomas that could be pharmacologically targeted by using a novel, selective small molecule inhibitor of the CREBBP/EP300 bromodomain. These data shed light on the unique roles of CREBBP and EP300 in the physiology and pathology of GC B cells, and provide a proof-of-principle for the development and testing of EP300 inhibition as a therapeutic strategy in these diseases.
2020-02-19 | GSE132365 | GEO
Project description:Various mechanisms have been reported to be responsible for enzalutamide resistance in prostate cancer. In our previous studies, we have demonstrated that the histone acetyltransferase EP300 is highly expressed in castration therapy-resistant prostate cancer. In the present study, we investigated the role of EP300/CREBBP in enzalutamide-resistant prostate cancer. Enzalutamide resistant and control DuCaP cells generatd previously were treated with histone acetyltransferase (C646) and bromodomain (I-CBP112) inhibitors of EP300/CREBBP. Additionally Enzalutamide resistant cells under 5 µM enzalutamide treatment and control LNCaP cells were analyzed. DuCaP and LNCaP cells were seeded in 6-well-plates at 8 x 10^5 and 6 x 10^5 cells per well. The following day, DuCaP cells were treated with 8 µM enzalutamide, 10 µM C646, 10 µM I-CBP112 or DMSO equivalent for 24 hr.
2021-02-17 | GSE163240 | GEO