Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1133054 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To date, most studies explored changes in 3D-genome organization between different tissues or during differentiation, which involve massive reprogramming of transcriptional programs. Much fewer studies examined alterations in genome organization in response to cellular stress, which involves less pervasive transcriptional modulation. Here, we examined associations between spatial chromatin organization and gene expression in two different biological contexts: transcriptional programs determining cell identity and transcriptional responses to stress, using p53 activation as a model. We selected 10 cell lines of diverse tissues, and in each performed micro-C, RNA-seq, and p53 ChIP-seq, before and after p53 induction. In the comparison between cell types, we delineated marked correlations between gene expression and spatial genome organization and identified hundreds of active enhancer–promoter loops associated with the expression of cell-type marker genes. In contrast, within each cell type, no such links were observed for expression changes induced by p53 activation, even for enhancers and promoters activated by p53 binding. Our analysis points to a fundamental difference between chromatin interactions that define cell identity and those that are established in response to cellular stress. Our results on p53-induced transcriptional responses support the recently proposed TF activity gradient model, which speculated a contact-independent mechanism for enhancer–promoter communication.
2025-07-10 | GSE278979 | GEO
Project description:To date, most studies explored changes in 3D-genome organization between different tissues or during differentiation, which involve massive reprogramming of transcriptional programs. Much fewer studies examined alterations in genome organization in response to cellular stress, which involves less pervasive transcriptional modulation. Here, we examined associations between spatial chromatin organization and gene expression in two different biological contexts: transcriptional programs determining cell identity and transcriptional responses to stress, using p53 activation as a model. We selected 10 cell lines of diverse tissues, and in each performed micro-C, RNA-seq, and p53 ChIP-seq, before and after p53 induction. In the comparison between cell types, we delineated marked correlations between gene expression and spatial genome organization and identified hundreds of active enhancer-promoter loops associated with the expression of cell-type marker genes. In contrast, within each cell type, no such links were observed for expression changes induced by p53 activation, even for enhancers and promoters activated by p53 binding. Our analysis points to a fundamental difference between chromatin interactions that define cell identity and those that are established in response to cellular stress. Our results on p53-induced transcriptional responses support the recently proposed TF activity gradient model, which speculated a contact-independent mechanism for enhancer-promoter communication.
2025-07-10 | GSE278978 | GEO
Project description:To date, most studies explored changes in 3D-genome organization between different tissues or during differentiation, which involve massive reprogramming of transcriptional programs. Much fewer studies examined alterations in genome organization in response to cellular stress, which involves less pervasive transcriptional modulation. Here, we examined associations between spatial chromatin organization and gene expression in two different biological contexts: transcriptional programs determining cell identity and transcriptional responses to stress, using p53 activation as a model. We selected 10 cell lines of diverse tissues, and in each performed micro-C, RNA-seq, and p53 ChIP-seq, before and after p53 induction. In the comparison between cell types, we delineated marked correlations between gene expression and spatial genome organization and identified hundreds of active enhancer-promoter loops associated with the expression of cell-type marker genes. In contrast, within each cell type, no such links were observed for expression changes induced by p53 activation, even for enhancers and promoters activated by p53 binding. Our analysis points to a fundamental difference between chromatin interactions that define cell identity and those that are established in response to cellular stress. Our results on p53-induced transcriptional responses support the recently proposed TF activity gradient model, which speculated a contact-independent mechanism for enhancer-promoter communication.
2025-07-10 | GSE278977 | GEO
Project description:Transcriptional programs of cell identity and p53-induced stress responses are associated with distinctive features of spatial genome organization [SuperSeries]
| PRJNA1169930 | ENA
Project description:The relationship between chromatin organization and transcriptional regulation is an area of intense investigation. We have characterized the spatial relationships between alleles of the Oct4, Sox2, and Nanog genes in single cells during the earliest stages of mouse embryonic stem cell (ESC) differentiation and during embryonic development. We describe homologous pairing of the Oct4 alleles during ESC differentiation and embryogenesis, and present evidence that pairing is correlated with the kinetics of ESC differentiation. Importantly, we identify critical DNA elements within the Oct4 promoter/enhancer region that mediate pairing of Oct4 alleles. Finally, we show that mutation of OCT4/SOX2 binding sites within this region abolishes inter-chromosomal interactions and affects accumulation of the repressive H3K9me2 modification at the Oct4 enhancer. Our findings demonstrate that chromatin organization and transcriptional programs are intimately connected in ESCs, and that the dynamic positioning of the Oct4 alleles is associated with the transition from pluripotency to lineage specification. Examination of chromatin contacts between Oct4 alleles using PE-4Cseq
2015-02-03 | E-GEOD-65510 | biostudies-arrayexpress
Project description:Embryonic stem cells (ESCs) cells run a self-renewal gene expression program, requiring the expression of certain transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs remains enigmatic. Here we show that Cohesin exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of the cohesin subunit Rad21 reveal an ESC specific cohesin binding pattern that is characterized by a CTCF independent colocalization of cohesin with pluripotency related transcription factors. Upon ESC differentiation, these binding sites disappear and instead new CTCF independent Rad21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of cohesin subunits causes expression changes that are reminiscent of the depletion of key pluripotency transcription factors, demonstrating the functional relevance of the cohesin - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin interacting proteins Stag1 and Wapl, further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2011-05-19 | E-GEOD-24030 | biostudies-arrayexpress
Project description:We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly though a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis. Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with microrarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system
2015-07-01 | E-GEOD-69108 | biostudies-arrayexpress
Project description:The coordinated differentiation of progenitor cells into specialized cell types and their spatial organization into distinct domains is central to embryogenesis. Here, we applied a new unbiased spatially resolved single-cell transcriptomics method to identify the genetic programs underlying the emergence of specialized cell types during limb development and their spatial integration. We identify multiple transcription factors whose expression patterns are predominantly associated with cell type specification or spatial position, suggesting two parallel yet highly interconnected regulatory systems. We demonstrate that the embryonic limb undergoes a complex multi-scale re-organization upon perturbation of one of its spatial organizing centers, including the loss of specific cell populations, specific alterations of pre-existing cell states’ molecular identities and changes in their relative spatial distribution. Our study shows how multi-dimensional single-cell, spatially resolved molecular atlases can allow the deconvolution of spatial identity and cell fate and reveal the interconnected genetic networks that regulate organogenesis and its reorganization upon genetic alterations.
2022-11-06 | GSE202326 | GEO
Project description:Primary outcome(s): The association between prognosis and circulating tumor DNA (p53, K-ras, B-raf, PIK3CA) and tumor DNA (p53, K-ras, B-raf, PIK3CA) in exosome before and after therapy including chemotherapy, chemoradiation therapy and surgery
| 2641208 | ecrin-mdr-crc
Project description:We compared Sox9-association at chondrocyte targets to a broad catalogue of regulatory indicators of chromatin organization and transcriptional activity to determine Sox9’s direct regulatory actions in normal developing chondrocytes. Sox9-associated regions resolve into two distinct regulatory categories. Class I regions closely associate with transcriptional start sites (TSSs). Their targets reflect general regulators of basal cell activities that Sox9 engages indirectly through a likely association with the basal transcriptional complex. In contrast, Class II regions outside of the local TSS domains highlight evolutionarily conserved, active enhancers directing expression of chondrocyte specific target genes, though DNA binding of Sox9-dimers at target sites with sub-optimal binding affinity. The level of associated chondrocyte gene expression correlates with the number of enhancer modules around the target gene and grouping into super-enhancer clusters. Comparison of Sox9 programs between neural crest and mesoderm-derived chondrocytes points to similar modes of chondrocyte specification in distinct chondrocyte lineages. These data provide the first insight into mammalian Sox family actions at the genome scale in the vivo setting. The resulting enhancer sets provide a key resource for further dissection of the regulatory programs of mammalian chondrogenesis. Incorportation of ChIP-seq data of Sox9 and histone modification marks for chromatin status together with micorarray gene expression profiling in neonatal mice chondrocytes to uncover Sox9 regulatory system. Overexpression of Sox9 with a control of EGFP in human fibroblasts to identify the direct targets of Sox9 regulatory system
2015-07-01 | E-GEOD-69110 | biostudies-arrayexpress