YY1 safeguard multidimensional epigenetic landscape associated with extended pluripotency
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PROVIDER: PRJNA662559 | ENA |
REPOSITORIES: ENA
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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:Totipotent cells with bidirectional chimeric ability attracts more attention from developmental biology and regenerative medicine. Human extended pluripotent stem cells can be obtained and maintained by converting conventional embryonic stem cells using the combo of chemicals, however, the transition and culture system is based on feeder and the mechanism during the acquisition of extended pluripotency is largely unknown. Here we first showed an adapted Matrigel-based feeder-free conversion and maintenance system to generate extended pluripotent stem cells from human embryonic stem cells. We demonstrated the extended pluripotency by molecular markers, chimeric ability and transcriptome. Our data provided an epigenetic and metabolic insight into the maintenance and transition of extended pluripotency.
2020-10-02 | GSE137208 | 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:Epigenetic and metabolic remodeling during the acquisition of extended pluripotency
| PRJNA564808 | ENA
Project description:Extended pluripotent stem cells (EPSCs) are a novel cell type derived from 8-cell stage embryo or conversion of pluripotent stem cells using a chemical cocktail that blocks the cell fate decision. Previous studies have defined various aspects of EPSCs including dual differentiational potency to both extraembryonic and embryonic lineages, their ability to directly transfer extended pluripotency to differentiated somatic cells by cell fusion remains unelucidated. Here, we sought to determine whether somatic cells could be reprogrammed and obtain extended pluripotency. In this study, newly derived EPSCs are fused with neural stem cells, which is somatic stem cells, by polyethylene glycol (PEG)-mediated method. The resulting hybrid cells exhibited pluripotential properties with upregulated EPSC-specific genes. Also, hybrid cells contributed to the embryonic and extraembryonic lineages in vivo and in vitro. RNA-sequencing analysis confirmed that the global gene expression pattern of hybrid cells are similar to EPSC while there is no expression of NSC markers, indicating complete erasure of somatic memory after fusion reprogramming. Lastly, EPSCs and hybrids exhibited a bivalent energy metabolism phenotype or more active oxidative phosphorylation (OXPHOS) and glycolysis than NSCs. In conclusion, the extended pluripotency of EPSCs could be transferred to somatic cells through fusion-induced reprogramming.
2022-08-07 | GSE210520 | GEO
Project description:CTCF is an architectural protein with a critical role in connecting higher-order chromatin folding in pluripotent stem cells. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. Here we set out to understand the extent to which shifts in genome-wide CTCF occupancy contribute to the 3-D reconfiguration of fine-scale chromatin folding during early neural lineage commitment. Unexpectedly, we observe a sharp decrease in CTCF occupancy during the transition from naïve/primed pluripotency to multipotent primary neural progenitor cells (NPCs). Many pluripotency gene-enhancer interactions are anchored by CTCF and its occupancy is lost in parallel with loop decommissioning during differentiation. Conversely, CTCF binding sites in NPCs are largely pre-existing in pluripotent stem cells. Only a small number of CTCF sites arise de novo in NPCs. We identify another zinc finger protein, Yin Yang 1 (YY1), at the base of looping interactions between NPC-specific genes and enhancers. Putative NPC-specific enhancers exhibit strong YY1 signal when engaged in 3-D contacts and negligible YY1 signal when not in loops. Moreover, siRNA knockdown of YY1 specifically disrupts interactions between key NPC enhancers and their target genes. YY1-mediated interactions between NPC regulatory elements are often nested within constitutive loops anchored by CTCF. Together, our results support a model in which YY1 acts as an architectural protein to connect developmentally regulated looping interactions; the location of YY1-mediated interactions may be demarcated in development by a pre-existing topological framework created by constitutive CTCF-mediated interactions.
2017-05-22 | GSE85185 | GEO
Project description:These data include the genome wide location analyses of Yy1 by bioChIPs of Fbio-Yy1. Streptavidin precipitation of formaldehyde cross-linked chromatin prepared from Fbio-Yy1 and control expressing mouse ES cells
2012-01-04 | E-GEOD-31785 | biostudies-arrayexpress
Project description:We mesured YY1 binding in isolated mouse crypt epihtelium using ChIP-seq Jejunal crypt epithelia were isolated and processed for ChIP using YY1 antibody Santa Cruz, SC-1703, lot E0511
2014-04-29 | E-GEOD-53502 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE31784: Expression changes in Yy1 knock down mouse embryonic stem cells GSE31785: Yy1 occupancy of mouse ES cell genome Refer to individual Series
2012-01-04 | E-GEOD-31786 | biostudies-arrayexpress
Project description:The DNA Guanine quadruplexes (G4) plays important roles in multiple cellular processes, including regulation of DNA replication, transcription and genome stability. Here, we show that Yin Yang-1 (YY1), a ubiquitously expressed and multifunctional transcription factor, can bind with G4 structures directly. Fluorescence anisotropy experiments shows that YY1 binds towards G4 structures with Kd in low nanomolar range (<100 nM) through the C terminal zinc finger domains. ChIP-seq results show that 81% of the YY1 ChIP-seq peaks contain G4 forming sequences, which is highly overlapped with the G4 ChIP-seq peaks. YY1 facilitate the DNA-DNA interaction through its binding with G4 structures in vivo and in vitro, which can be disturbed by G4 stabilizer treatment. In all, our studies identify a novel G4 structure binding protein-YY1, and reveal that G4 structure functions in DNA-DNA interaction.
2020-08-27 | GSE128106 | GEO