YY1 complex in tumor-associated macrophage promotes prostate cancer progression by upregulating IL-6 [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA827701 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tumor-associated macrophages are mainly polarized into the M2 phenotype, which remodels the tumor microenvironment and promotes tumor progression by secreting various cytokines. Herein, we reported that Yin Yang 1 (YY1) was highly expressed on tumor-infiltrated M2 macrophages in prostate cancer and was associated with poorer clinical outcomes. Using transgenic mice overexpressing YY1, we found that the tumor-promoting effects of oe-YY1 mice could be suppressed by macrophage depletion. Further in-vitro and in-vivo experiments using YY1 overexpressing and knocked down M2 macrophages demonstrated that YY1 induced M2 polarization and increased macrophages-induced prostate cancer progression by the IL-6/STAT3 pathway. Furthermore, YY1 promoted phase-separated condensates and upregulated IL-6 by modulating p300, p300 and CEBPB as a transcription complex. By conducting chromatin immunoprecipitation sequencing of M2 macrophages and monocytes, an M2-specific IL-6 enhancer associated with the YY1 complex was shown to upregulate IL-6 expression in M2 macrophages, and H3K27ac and YY1 signals significantly increased around this enhancer. In conclusion, YY1 complex promotes the M2 macrophages polarization and upregulates IL-6 in macrophages by inducing phase separation and a M2-specific enhancer, thereby increasing prostate cancer progression. These findings might lead to novel therapies targeting YY1 in prostate tumor-associated macrophages.
2023-04-01 | GSE200948 | GEO
Project description:Tumor-associated macrophages are mainly polarized into the M2 phenotype, which remodels the tumor microenvironment and promotes tumor progression by secreting various cytokines. Herein, we reported that Yin Yang 1 (YY1) was highly expressed on tumor-infiltrated M2 macrophages in prostate cancer and was associated with poorer clinical outcomes. Using transgenic mice overexpressing YY1, we found that the tumor-promoting effects of oe-YY1 mice could be suppressed by macrophage depletion. Further in-vitro and in-vivo experiments using YY1 overexpressing and knocked down M2 macrophages demonstrated that YY1 induced M2 polarization and increased macrophages-induced prostate cancer progression by the IL-6/STAT3 pathway. Furthermore, YY1 promoted phase-separated condensates and upregulated IL-6 by modulating p300, NF-κB and CEBPB as a transcription complex. By conducting chromatin immunoprecipitation sequencing of M2 macrophages and monocytes, an M2-specific IL-6 enhancer associated with the YY1 complex was shown to upregulate IL-6 expression in M2 macrophages, and H3K27ac and YY1 signals significantly increased around this enhancer. In conclusion, YY1 complex promotes the M2 macrophages polarization and upregulates IL-6 in macrophages by inducing phase separation and a M2-specific enhancer, thereby increasing prostate cancer progression. These findings might lead to novel therapies targeting YY1 in prostate tumor-associated macrophages.
2023-04-01 | GSE200947 | GEO
Project description:YY1 complex in tumor-associated macrophage promotes prostate cancer progression by upregulating IL-6
| PRJNA827698 | ENA
Project description:YY1 complex in tumor-associated macrophage promotes prostate cancer progression by upregulating IL-6 [ChIP-seq]
| PRJNA827702 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-04-01 | GSE200949 | GEO
Project description:Although extended pluripotent stem cells (EPSCs) have the potential to form both embryonic and extraembryonic lineages, how their transcriptional regulatory mechanism differs from that of embryonic stem cells (ESCs) remains unclear. Here, we discovered that YY1 binds to specific open chromatin regions in EPSCs. Yy1 depletion in EPSCs leads to a gene expression pattern more similar to that of ESCs than control EPSCs. Moreover, Yy1 depletion triggers a series of epigenetic crosstalk activities, including changes in DNA methylation, histone modifications and high-order chromatin structures. Yy1 depletion in EPSCs disrupts the enhancer-promoter (EP) interactions of EPSC-specific genes, including Dnmt3l. Yy1 loss results in DNA hypomethylation and dramatically reduces the enrichment of H3K4me3 and H3K27ac on the promoters of EPSC-specific genes by upregulating the expression of Kdm5c and Hdac6 through facilitating the formation of CCCTC-binding factor (CTCF)-mediated EP interactions surrounding their loci. Furthermore, single-cell RNA sequencing (scRNA-seq) experiments revealed that YY1 is required for the derivation of extraembryonic endoderm (XEN)-like cells from EPSCs in vitro. Together, this study reveals that YY1 functions as a key regulator of multidimensional epigenetic crosstalk associated with extended pluripotency.
2022-04-18 | GSE157720 | GEO
Project description:YY1 is a ubiquitously expressed, intrinsically disordered transcription factor involved in neural development. The oligomeric state of YY1 varies depending on the environment. These changes may alter its DNA binding ability and hence its transcriptional activity. In addition to its oligomeric state, the interaction of YY1 with proteins such as FOXP2 can impact its role in transcription. The aim of this work is to study the structure and dynamics of YY1 binding to DNA and to determine the influence of oligomerisation and associations with FOXP2 on its DNA binding mechanism. Size exclusion chromatography, fluorescence anisotropy and electrophoretic mobility shift assays were used to study YY1 oligomerisation and interaction with FOXP2. To better understand potential structural changes to YY1 upon DNA binding, hydrogen deuterium exchange mass spectrometry was used. The results indicate that YY1 consists of specific structured regions, while most of the sequence remains disordered. Furthermore, the oligomeric nature of the protein is dependent on ionic strength. DNA affects oligomerisation and the protein undergoes changes in structure and dynamics upon DNA binding. YY1 and FOXP2 were found to interact with each other both in isolation and in the presence of YY1-specific DNA. The heterogeneous, dynamic multimerisation of YY1 identified in this work is, therefore, likely to be important for its ability to make heterologous associations with other proteins such as FOXP2. The interactions that YY1 forms with itself, FOXP2 and DNA form part of an intricate mechanism of transcriptional regulation by YY1, which is vital for appropriate neural development.
2024-01-26 | PXD038431 | Pride
Project description:Serine metabolism supports macrophage IL-1β production.
| PRJNA515004 | ENA
Project description:Interleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome wide association studies and experimental animal models point at a central role of the IL-10 axis in Inflammatory Bowel Diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10R?) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1hi-expressingmacrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages, but resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning factor in the colon and define intestinal CX3CR1hi macrophages as a decisive factor that determines gut health or inflammation. Microarray of resident macrophages sorted from colons of Interleukin-10 deficeint mice and macrophage-restricted interleukin-10 receptor deficient mice versus colonic resident macrophages of wild type mice
2014-05-09 | E-GEOD-56444 | biostudies-arrayexpress
Project description:Evaluation of the changes in glycosylation induced by IL-4 alternative macrophage activation
2011-04-29 | GSE28929 | GEO