The EZH2-PRC2-H3K27me3 axis governing the endometrial cell cycle and differentiation for successful blastocyst invasion
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE207362 | GEO | 2023/05/15
REPOSITORIES: GEO
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Project description:The EZH2-PRC2-H3K27me3 axis governing the endometrial cell cycle and differentiation for successful blastocyst invasion
| PRJNA854933 | ENA
Project description:A lysine-to-methionine mutation at lysine 27 of histone 3 (H3K27M) has been shown to promote oncogenesis in a subset of pediatric gliomas. While there is evidence that this "oncohistone" mutation acts by inhibiting the histone methyltransferase PRC2, the details of this proposed mechanism nevertheless continue to be debated. Recent evidence suggests that PRC2 must simultaneously bind both H3K27M and H3K27me3 to experience competitive inhibition of its methyltransferase activity. In this work, we used PRC2 inhibitor treatments in a transgenic H3K27M cell line to validate this dependence in a cellular context. We further used designer chromatin inhibitors to probe the geometric constraints of PRC2 engagement of H3K27M and H3K27me3 in a biochemical setting. We found that PRC2 binds to a bivalent inhibitor unit consisting of an H3K27M and an H3K27me3 nucleosome and exhibits a distance dependence in its affinity for such an inhibitor, which favors closer proximity of the 2 nucleosomes within a chromatin array. Together, our data precisely delineate fundamental aspects of the H3K27M inhibitor and support a model wherein PRC2 becomes trapped at H3K27M-H3K27me3 boundaries.
| S-EPMC6825254 | biostudies-literature
Project description:Comparative trascriptomic analysis between porcine early-blastocyst and Hatched blastocyst collected around day 5-6 direct comparison with dye-swap; two different arrays with 6 Samples each
2015-06-21 | E-GEOD-38882 | biostudies-arrayexpress
Project description:Comparative trascriptomic analysis between porcine early-blastocyst and Hatched blastocyst collected around day 5-6
2015-06-21 | GSE38882 | GEO
Project description:The polycomb repressive complex 2 (PRC2) catalyzes the methylation of histone H3 on lysine 27 (H3K27) to generate trimethyl-H3K27 (H3K27me3) marks, thereby leading to a repressive chromatin state that inhibits gene expression. C10ORF12 was recently identified as a novel PRC2 interactor. Here, we show that C10ORF12 specifically interacts with PRC2 through its middle region (positions 619-718). C10ORF12 significantly enhances the histone methyltransferase activity of PRC2 in vitro and dramatically increases the total H3K27me3 levels in HeLa cells. C10ORF12 also antagonizes Jarid2, which is an auxiliary factor of the PRC2.2 subcomplex, to promote increased H3K27me3 levels in HeLa cells. Moreover, C10ORF12 alters the substrate preference of PRC2. These results indicate that C10ORF12 functions as a positive regulator of PRC2 and facilitates PRC2-mediated H3K27me3 modification of chromatin. These findings provide new insight into the roles of C10ORF12 in regulating the activity of the PRC2 complex.
| S-EPMC6889301 | biostudies-literature
Project description:Functional profile of bovine blastocyst-derived trophoblast cells
2018-11-13 | MSV000083135 | MassIVE
Project description:Polycomb Group (PcG) proteins maintain transcriptional repression throughout development, mostly by regulating chromatin structure. Polycomb Repressive Complex 2 (PRC2), a component of the Polycomb machinery, is responsible for the methylation of histone H3 lysine 27 (H3K27me2/3). Jarid2 was previously identified as a cofactor of PRC2, regulating PRC2 targeting to chromatin and its enzymatic activity. Deletion of Jarid2 leads to impaired orchestration of gene expression during cell lineage commitment. Here, we reveal an unexpected crosstalk between Jarid2 and PRC2, with Jarid2 being methylated by PRC2. This modification is recognized by the Eed core component of PRC2 and triggers an allosteric activation of PRC2's enzymatic activity. We show that Jarid2 methylation is important to promote PRC2 activity at a locus devoid of H3K27me3 and for the correct deposition of this mark during cell differentiation. Our results uncover a regulation loop where Jarid2 methylation fine-tunes PRC2 activity depending on the chromatin context.
| S-EPMC4352895 | biostudies-other
Project description:Background:EZH2 acts as an oncogene through canonical pathway EZH2/H3K27Me3 and uncanonical pathway pAkt1/pS21EZH2 in many solid tumors including ovarian cancer. However, the clinical value of EZH2/H3K27Me3 and pAkt1/pS21EZH2 remain unclear. In the current study, we aim to investigate the correlation between these two pathways to clinical-pathological parameters and prognosis. Methods:EZH2, H3K27Me3, pAkt1 and pS21EZH2 expression were evaluated by tissue micro-array and immunohistochemistry in a cohort of ovarian cancer patients. The results were analyzed based on clinical characteristics and survival outcomes. Results:EZH2, H3K27Me3, pAkt1 and pS21EZH2 were universally expressed in ovarian cancer specimens with a positive expression rate of 81.54% (53/65), 88.89% (48/54), 63.07% (41/65) and 75.38% (49/65). EZH2-pS21EZH2 (Spearman r = 0.580, P < 0.0001) and pS21EZH2-pAkt1 (Spearman r = 0.546, P < 0.0001) were closely correlated while EZH2- H3K27Me3 were less closely correlated (Spearman r = 0.307, P = 0.002). Low pS21EZH2 associated with better chemotherapy response (OR = 0.184; 95% CI [0.052-0.647], P = 0.008) according to logistic regression with an area under the curve of 0.789 (specificity 89.36%, sensitivity 68.42%) by ROC analysis and predicted improved progression-free survival (HR = 0.453; 95% CI [0.229-0.895], P = 0.023) as indicated by multivariate cox regression. A combination of EZH2low/H3K27Me3low status predicted better chemotherapy response (OR = 0.110; 95% CI [0.013-0.906], P = 0.040) and better progression-free survival (HR = 0.388; 95% CI [0.164-0.917], P = 0.031). The results suggested that EZH2/H3K27Me3 and pEZH2 predicted chemotherapy response and progression-free survival in ovarian cancer.
| S-EPMC7227641 | biostudies-literature
Project description:In this study we aimed to examine the effect of alternative in vivo and in vitro culture conditions during the time of blastocyst formation on the transcriptome profile of bovine blastocysts. Two different blastocyst groups were produced. The first group (Vitro_morula) was matured, fertilized and cultured in vitro until morula stage then transferred to synchronized recipients and blastocysts were collected at day 7 by uterine flushing. The second group (Vivo_morula) was matured, fertilized and cultured in vivo until morula stage then flushed out and cultured in vitro until day 7. Complete in vitro (IVP) and in vivo blastocysts were produced and used as controls.
2014-01-30 | E-GEOD-49391 | biostudies-arrayexpress
Project description:Little is understood about the embryonic development of sociality. We screened 1120 known drugs and found that embryonic inhibition of topoisomerase IIα (Top2a) resulted in lasting social deficits in zebrafish. In mice, prenatal Top2 inhibition caused defects in social interaction and communication, which are behaviors that relate to core symptoms of autism. Mutation of Top2a in zebrafish caused down-regulation of a set of genes highly enriched for genes associated with autism in humans. Both the Top2a-regulated and autism-associated gene sets have binding sites for polycomb repressive complex 2 (PRC2), a regulatory complex responsible for H3K27 trimethylation (H3K27me3). Moreover, both gene sets are highly enriched for H3K27me3. Inhibition of the PRC2 component Ezh2 rescued social deficits caused by Top2 inhibition. Therefore, Top2a is a key component of an evolutionarily conserved pathway that promotes the development of social behavior through PRC2 and H3K27me3.
| S-EPMC9683714 | biostudies-literature