Direct neuronal reprogramming of mouse astrocytes is associated with multiscale epigenome remodeling and requires Yy1
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ABSTRACT:
PROVIDER: PRJNA860940 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20341400_1.fastq.gz | Fastqsanger.gz | |||
| SRR20341400_2.fastq.gz | Fastqsanger.gz | |||
| SRR20341401_1.fastq.gz | Fastqsanger.gz | |||
| SRR20341401_2.fastq.gz | Fastqsanger.gz | |||
| SRR20341402_1.fastq.gz | Fastqsanger.gz |
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Project description:Direct neuronal reprogramming is a promising approach to regenerate neurons from local glial cells. However, mechanisms of epigenome remodeling and co-factors facilitating this process are unclear. Here, we combine single-cell multiomics with genome-wide profiling of 3D nuclear architecture and DNA methylation in mouse astrocyte-to-neuron reprogramming mediated by Neurogenin2 (Ngn2) and its phosphorylation-resistant form (PmutNgn2), respectively. We show that Ngn2 drives multilayered chromatin remodelling at dynamic enhancer-gene interaction sites. PmutNgn2 leads to higher reprogramming efficiency and enhances epigenetic remodeling associated with neuronal maturation. However, the differences in binding sites or downstream gene activation cannot fully explain this effect. Instead, we identify Yy1, a transcriptional co-factor, recruited by direct interaction with Ngn2 to its target sites. Upon deletion of Yy1, activation of neuronal enhancers, genes, and ultimately reprogramming are impaired without affecting Ngn2 binding. Thus, our work highlights the key role of interactors of proneural factors in direct neuronal reprogramming.
2024-04-30 | GSE208742 | 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: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
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2013-12-01 | E-GEOD-36145 | biostudies-arrayexpress
Project description:Direct cell reprogramming has enabled the direct conversion of skin fibroblasts into functional neurons and oligodendrocytes using a minimal set of cell lineage-specific transcription factors. This approach has substantial advantages since it is rapid and simple, generating the cell type of interest in a single step. However, it remains unknown whether this technology can be applied for directly reprogramming skin cells into astrocytes, the third neural lineage. Astrocytes play crucial roles in neuronal homeostasis and their dysfunctions contribute to the origin and progression of multiple human diseases. Herein, we carried out a screening using several transcription factors involved in defining the astroglial cell fate and identified NFIA, NFIB and SOX9 to be sufficient to convert with high efficiency embryonic and post-natal mouse fibroblasts into astrocytes (iAstrocytes). We proved both by gene expression profiling and functional tests that iAstrocytes are comparable to native brain astrocytes. This protocol can be then employed to generate functional iAstrocytes for a wide range of experimental applications. Induced astrocytes (iAstro) were compared to Fibroblasts (Fibro) as negative control and to primary astrocytes (astro) as positive control. Three biological replicates were analyzed for each experimental group.
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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:Epithelial–mesenchymal transition (EMT) is an important mechanism of metastasis and malignant progression of hepatocellular carcinoma (HCC). However, the transcriptional regulation mechanism of EMT remains poorly understood. Some transcriptional co-activators can form phase-separated condensates at super-enhancers that compartmentalize and concentrate the transcription apparatus to drive robust gene expression. Here, we demonstrate that Twist1 and YY1, interact with p300 and form phase-separated local high-concentration interaction hubs at super-enhancers of miRNA-9 and activate its expression to induce EMT and promote the malignant evolution of HCC. Phase separation disrupted by metformin perturbs Twist–YY1 condensates, thereby inhibiting EMT. To explore how the Twist1 complex regulates miR-9 expression by binding SE region, we performed Twist1 ChIP-seq combined with H3K4me3, H3K4me1, H3K27ac, DNAse, p300, and YY1 ChIP-seq data to detect the SEs of miR-9. After metformin treatment, the peak of Twist1/YY1 on miR-9 SE decreased. Metformin specifically affects the binding of Twist1/YY1 to the miR-9 SE region. 1,6-hexanediol, as an aliphatic alcohol, can weaken hydrophobic interactions and inhibit liquid–liquid phase separation by disrupting hydrophobic interactions. In order to prove Twist1/YY1 interaction at these sites requires phase separation, we detect the accessibility of miR-9 SE regions in 1,6-hexanediol-treated cells. The result showed a general decrease in the accessibility of miR-9 super-enhancer regions in 1,6-hexanediol-treated cells and Twist1 / YY1 combines the SE region of miR-9 in the form of phase separation.
2019-12-13 | GSE141965 | GEO
Project description:Ectopic expression of the reprogramming factors OCT4, SOX2, or NANOG into human astrocytes in specific cytokine/culture conditions activated the neural stem gene program and induced generation of cells expressing neural stem/precursor markers (ASTRO-NSC). To evaluate the epigenetic changes associated with this reprogramming, we analyzed the DNA methylation patterns of Astro-NSC relative to untransfected astrocytes. We compared three human AstroNANOG-NSC clones to the astrocytes from which they were derived using NimbleGen 3x720K CpG Island Plus RefSeq Promoter Arrays
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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
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Project description:By applying ChIP-seq, we generated genome-wide maps of YY1 in skeletal myoblasts and myotubes. We found that YY1 binds to 1820 confident target with a large portion residing in the intergenic regions. In addition, YY1 was found to activate many loci, and there is no significant overlap between YY1 and Ezh2 targets, suggensting a Ezh2-independent manner. Further detailed study revealed that YY1 can regulate some lincRNAs which are fucntional in skeletal myogenesis. In this study, we identified a YY1-Yam-1-miR-715 (TF-lincRNA-miRNA) regulatory curcuit in myogensis. Examination of YY1 targets in myoblast versus myotubes
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