Chromatin factor YY1 controls fetal hematopoietic stem cell migration and engraftment in mice [CUT&Tag]
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PROVIDER: PRJNA1174796 | ENA |
REPOSITORIES: ENA
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Project description:Fetal liver is a major organ for generating hematopoietic stem cells (HSCs) during embryonic development. Many questions remain unanswered regarding how transition of hematopoiesis from the fetal liver to the bone marrow (BM) is regulated. We demonstrate that mammalian Polycomb Group (PcG) protein Yin Yang 1 (YY1) is required for this transition, as a conditional knockout of Yy1 in the hematopoietic system during fetal development results in exhaustion of fetal HSC pools and neonatal death. Yy1 deficient fetal HSCs have diminished capacity to migrate to and engraft the adult BM, and consequently fail to reconstitute blood. YY1 deficiency leads to distinct transcriptomic changes in fetal hematopoietic stem progenitor cells (HSPCs) compared with adult HSPCs. The genetic networks governing cell motility and adhesion are distinctly deregulated by YY1 in fetal HSPCs. Notably, YY1 regulates mobility of fetal HSPCs largely through an indirect mechanism as it does not directly bind to the promoters of dysregulated genes involved in control of mobility. Instead, it regulates broader transcriptional mechanisms by modulating the genes in chromatin remodeling complexes that impact HSPC mobility. Our study provides a framework to further decipher how temporal epigenomic configurations determine HSC fetal-to-adult transition during development.
2025-07-11 | GSE279863 | GEO
Project description:Fetal liver is a major organ for generating hematopoietic stem cells (HSCs) during embryonic development. Many questions remain unanswered regarding how transition of hematopoiesis from the fetal liver to the bone marrow (BM) is regulated. We demonstrate that mammalian Polycomb Group (PcG) protein Yin Yang 1 (YY1) is required for this transition, as conditional knockout of Yy1 in the hematopoietic system during fetal development results in exhaustion of fetal HSC pools and is associated with neonatal death. Yy1 deficient fetal HSCs have diminished capacity to migrate to and engraft the adult BM, and consequently fail to reconstitute blood. The genetic networks governing cell motility and adhesion are distinctly deregulated by YY1 knockout in fetal HSPCs. Notably, YY1 regulates mobility of fetal HSPCs largely through an indirect mechanism as it does not directly bind to the promoters of dysregulated genes involved in control of cell mobility. Instead, it regulates broader transcriptional mechanisms by regulating the genes in chromatin remodeling complexes and modulating chromatin accessibility that impact HSPC migration. Our study provides a framework to further decipher how temporal epigenomic configurations determine HSC fetal-to-adult transition during development.
2025-07-11 | GSE298778 | GEO
Project description:Fetal liver is a major organ for generating hematopoietic stem cells (HSCs) during embryonic development. Many questions remain unanswered regarding how transition of hematopoiesis from the fetal liver to the bone marrow (BM) is regulated. We demonstrate that mammalian Polycomb Group (PcG) protein Yin Yang 1 (YY1) is required for this transition, as a conditional knockout of Yy1 in the hematopoietic system during fetal development results in exhaustion of fetal HSC pools and neonatal death. Yy1 deficient fetal HSCs have diminished capacity to migrate to and engraft the adult BM, and consequently fail to reconstitute blood. YY1 deficiency leads to distinct transcriptomic changes in fetal hematopoietic stem progenitor cells (HSPCs) compared with adult HSPCs. The genetic networks governing cell motility and adhesion are distinctly deregulated by YY1 in fetal HSPCs. Notably, YY1 regulates mobility of fetal HSPCs largely through an indirect mechanism as it does not directly bind to the promoters of dysregulated genes involved in control of mobility. Instead, it regulates broader transcriptional mechanisms by modulating the genes in chromatin remodeling complexes that impact HSPC mobility. Our study provides a framework to further decipher how temporal epigenomic configurations determine HSC fetal-to-adult transition during development.
2025-07-11 | GSE279864 | GEO
Project description:Chromatin factor YY1 controls fetal hematopoietic stem cell migration and engraftment in mice [RNA-seq]
| PRJNA1174800 | ENA
Project description:Chromatin factor YY1 controls fetal hematopoietic stem cell migration and engraftment in mice [ATAC-seq]
| PRJNA1271089 | ENA
Project description:Extrachromosomal DNA (ecDNA) is an important carrier for the amplification of proto-oncogenes. It can not only drive cancer progression by increasing the copy number of oncogenes but also influence the transcriptional regulation of oncogenes by increasing chromatin accessibility and regulating chromatin interactions. Currently, the generation of ecDNA is rather complex and the exact mechanism remains unclear. This study aims to investigate the molecular mechanism underlying the generation of ecDNA in order to identify the targets for ecDNA-targeted drug therapies. We analyzed the chromatin landscape in COLO320-DM and COLO320-HSR cells through CUT&Tag. The results of CUT&Tag for Lig3, the open chromatin marker H3K27ac, and the promoter marker H3K4me3 showed that Lig3 was specifically enriched in the MYC ecDNA amplification regions and bound to a large number of open chromatin regions and promoter regions, indicating that Lig3 may be related to the formation of ecDNA and stably bind to ecDNA, thereby maintaining the integrity of the genes carried by ecDNA. Furthermore, we found that there were a large number of merge peaks between Lig3 and YY1 across the whole genome, which were abundantly occupied at the MYC ecDNA amplification sites. Meanwhile, we observed that in COLO320-DM cells (where oncogenes are amplified in the form of ecDNA), there was a significant enrichment of YY1 in the MYC amplification regions, while in COLO320-HSR cells (where oncogenes are amplified on the homogeneously staining regions, HSR), the peaks of YY1 were significantly decreased. Our data suggest that YY1 is essential for the generation of ecDNA. It forms a complex with Lig3 to jointly regulate the formation of ecDNA, and this complex can be detected as it resides on ecDNA for a relatively long period of time. This may also be related to the stability of ecDNA and its involvement in genomic regulation.
2025-07-25 | GSE287200 | GEO
Project description:The protein Yin-Yang 1 (YY1) is a ubiquitous multifunctional transcription factor. Interestingly, there are several cellular functions controlled by YY1 that could play a role in Leishmania pathogenesis. Leishmaniasis is a human disease caused by protozoan parasites of the genus Leishmania. This study examined the potential role of macrophage YY1 in promoting Leishmania intracellular survival. Knockdown of YY1 resulted in attenuated survival of Leishmania in infected macrophages, suggesting a role of YY1 in Leishmania persistence. Biochemical fractionation studies revealed Leishmania infection caused redistribution of YY1 to the cytoplasm from the nucleus where it is primarily located. Inhibition of nuclear transport by leptomycin B attenuates infection-mediated YY1 redistribution and reduces Leishmania survival. This suggests that Leishmania induces the translocation of YY1 from the nucleus to the cytoplasm of infected cells, where it may regulate host molecules to favour parasite survival. A label-free quantitative whole proteome approach showed that the expression of a large number of macrophage proteins was dependent on the YY1 level. Interestingly, several of these proteins were modulated in Leishmania-infected cells, revealing YY1-dependent host response and suggesting their potential role in Leishmania pathogenesis. Together, these findings identify YY1 as a novel and essential virulence factor by proxy that promotes Leishmania survival.
2025-03-14 | PXD059968 | Pride
Project description:YY1 and Lig3 collaboratively regulate ecDNA biogenesis (CUT&Tag)
| PRJNA1211587 | ENA
Project description:YY1 is a sequence-specific DNA-binding transcription factor that has many important biological roles. However, its function in trophoblasts at the maternal-foetal interface remains to be elucidated. In this study, we used an mRNA microarray and quantitative reverse transcription-PCR and compared the YY1 mRNA expression level in trophoblasts between patients with recurrent miscarriage (RM) and healthy control subjects. Our results revealed that YY1 mRNA expression was significantly lower in the trophoblasts of the RM group compared with the healthy control group. Furthermore, immunofluorescence and immunohistochemical data showed that YY1 was highly expressed in human placental villi during early pregnancy, especially in cytotrophoblast cells and invasive extravillous trophoblasts, and it was expressed at a much lower level in the placental villi of term pregnancy. YY1 overexpression enhanced the invasion and proliferation of trophoblasts, while knockdown of YY1 repressed these effects. Antibody array screening revealed that YY1 significantly promoted MMP2 expression in trophoblasts. Bioinformatics analysis identified three YY1-binding sites in the MMP2 promoter region, and chromatin immunoprecipitation analysis verified that YY1 binds directly to its promoter region. Importantly, inhibition of YY1 by siRNA clearly decreased trophoblast invasion in an ex vivo explant culture model. Overall, our findings revealed a new regulatory pathway of YY1/MMP2 in trophoblast cells invasion during early pregnancy, and indicated that YY1 may be involved in the pathogenesis of RM. Total RNA was isolated using Trizol from trophoblast cells from three healthy controls (HC) and three recurrent miscarriage (RM) patients. Total RNA were extracted and used for hybridizing Affymetrix chips (GeneChip® Human Transcriptome Array 2.0(HTA2.0)). Data were normalised by gcRMA method and raw p-values adjusted by Bonferroni procedure (1%).
2016-01-21 | E-GEOD-76862 | biostudies-arrayexpress
Project description:YY1 is a sequence-specific DNA-binding transcription factor that has many important biological roles. However, its function in trophoblasts at the maternal-foetal interface remains to be elucidated. In this study, we used an mRNA microarray and quantitative reverse transcription-PCR and compared the YY1 mRNA expression level in trophoblasts between patients with recurrent miscarriage (RM) and healthy control subjects. Our results revealed that YY1 mRNA expression was significantly lower in the trophoblasts of the RM group compared with the healthy control group. Furthermore, immunofluorescence and immunohistochemical data showed that YY1 was highly expressed in human placental villi during early pregnancy, especially in cytotrophoblast cells and invasive extravillous trophoblasts, and it was expressed at a much lower level in the placental villi of term pregnancy. YY1 overexpression enhanced the invasion and proliferation of trophoblasts, while knockdown of YY1 repressed these effects. Antibody array screening revealed that YY1 significantly promoted MMP2 expression in trophoblasts. Bioinformatics analysis identified three YY1-binding sites in the MMP2 promoter region, and chromatin immunoprecipitation analysis verified that YY1 binds directly to its promoter region. Importantly, inhibition of YY1 by siRNA clearly decreased trophoblast invasion in an ex vivo explant culture model. Overall, our findings revealed a new regulatory pathway of YY1/MMP2 in trophoblast cells invasion during early pregnancy, and indicated that YY1 may be involved in the pathogenesis of RM.
2016-01-21 | GSE76862 | GEO