Similar Datasets
Project description:Little is known about how three-dimensional chromatin topology shapes mammalian craniofacial development. In mouse cranial neural crest cells, a Polycomb Repressive Complex 2 (PRC2)-dependent chromatin architecture is established before migration. This configuration maintains craniofacial gene promoters poised and connects them with distal Polycomb tethering elements, positioning promoters in spatial proximity to future long-range enhancers. Deletion of Ezh2 disrupts this early topology, causing inappropriate gene derepression in post-migratory craniofacial subpopulations where these genes are normally silenced, and failure of long-range enhancer recruitment where activation is required, thereby impairing proper gene expression. We further identify a distal Polycomb tethering element essential for Hoxa2 enhancer recruitment across topologically associating domains. Thus, Polycomb acts not only as a transcriptional repressor, but also as a chromatin-folding organizer that prepares developmental genes for later activation, by facilitating subsequent recruitment of distal active enhancers previously not in contact. Polycomb-mediated topology therefore orchestrates the transition from progenitor plasticity to precise spatiotemporal control of morphogenetic gene programs during neural crest development and face formation.
2026-04-08 | GSE295407 | GEO
Project description:Little is known about how three-dimensional chromatin topology shapes mammalian craniofacial development. In mouse cranial neural crest cells, a Polycomb Repressive Complex 2 (PRC2)-dependent chromatin architecture is established before migration. This configuration maintains craniofacial gene promoters poised and connects them with distal Polycomb tethering elements, positioning promoters in spatial proximity to future long-range enhancers. Deletion of Ezh2 disrupts this early topology, causing inappropriate gene derepression in post-migratory craniofacial subpopulations where these genes are normally silenced, and failure of long-range enhancer recruitment where activation is required, thereby impairing proper gene expression. We further identify a distal Polycomb tethering element essential for Hoxa2 enhancer recruitment across topologically associating domains. Thus, Polycomb acts not only as a transcriptional repressor, but also as a chromatin-folding organizer that prepares developmental genes for later activation, by facilitating subsequent recruitment of distal active enhancers previously not in contact. Polycomb-mediated topology therefore orchestrates the transition from progenitor plasticity to precise spatiotemporal control of morphogenetic gene programs during neural crest development and face formation.
2026-04-08 | GSE295406 | GEO
Project description:Little is known about how three-dimensional chromatin topology shapes mammalian craniofacial development. In mouse cranial neural crest cells, a Polycomb Repressive Complex 2 (PRC2)-dependent chromatin architecture is established before migration. This configuration maintains craniofacial gene promoters poised and connects them with distal Polycomb tethering elements, positioning promoters in spatial proximity to future long-range enhancers. Deletion of Ezh2 disrupts this early topology, causing inappropriate gene derepression in post-migratory craniofacial subpopulations where these genes are normally silenced, and failure of long-range enhancer recruitment where activation is required, thereby impairing proper gene expression. We further identify a distal Polycomb tethering element essential for Hoxa2 enhancer recruitment across topologically associating domains. Thus, Polycomb acts not only as a transcriptional repressor, but also as a chromatin-folding organizer that prepares developmental genes for later activation, by facilitating subsequent recruitment of distal active enhancers previously not in contact. Polycomb-mediated topology therefore orchestrates the transition from progenitor plasticity to precise spatiotemporal control of morphogenetic gene programs during neural crest development and face formation.
2026-04-08 | GSE295340 | GEO
Project description:Little is known about how three-dimensional chromatin topology shapes mammalian craniofacial development. In mouse cranial neural crest cells, a Polycomb Repressive Complex 2 (PRC2)-dependent chromatin architecture is established before migration. This configuration maintains craniofacial gene promoters poised and connects them with distal Polycomb tethering elements, positioning promoters in spatial proximity to future long-range enhancers. Deletion of Ezh2 disrupts this early topology, causing inappropriate gene derepression in post-migratory craniofacial subpopulations where these genes are normally silenced, and failure of long-range enhancer recruitment where activation is required, thereby impairing proper gene expression. We further identify a distal Polycomb tethering element essential for Hoxa2 enhancer recruitment across topologically associating domains. Thus, Polycomb acts not only as a transcriptional repressor, but also as a chromatin-folding organizer that prepares developmental genes for later activation, by facilitating subsequent recruitment of distal active enhancers previously not in contact. Polycomb-mediated topology therefore orchestrates the transition from progenitor plasticity to precise spatiotemporal control of morphogenetic gene programs during neural crest development and face formation.
2026-04-08 | GSE295473 | GEO
Project description:Polycomb-group proteins play critical roles in gene silencing through the deposition of histone H3 lysine 27 trimethylation (H3K27me3) and chromatin compaction. This process is essential for embryonic stem cell (ESC) pluripotency, differentiation, and development. Polycomb repressive complex 2 (PRC2) can both read and write H3K27me3, enabling progressive spreading of H3K27me3 on the linear genome. Long-range Polycomb-associated DNA contacts have also been described, but their regulation and role in gene silencing remain unclear. Here, we apply H3K27me3 HiChIP, a protein-directed chromosome conformation method, and optical reconstruction of chromatin architecture to profile long-range Polycomb-associated DNA loops that span tens to hundreds of megabases across multiple topological associated domains in mouse ESCs and human induced pluripotent stem cells. We find that H3K27me3 loop anchors are enriched for Polycomb nucleation points and coincide with key developmental genes. Genetic deletion of H3K27me3 loop anchors results in disruption of spatial contact between distant loci and altered H3K27me3 in cis, both locally and megabases away on the same chromosome. In mouse embryos, loop anchor deletion leads to ectopic activation of the partner gene, suggesting that Polycomb-associated loops control gene silencing during development. Further, we find that alterations in PRC2 occupancy resulting from an RNA binding–deficient EZH2 mutant are accompanied by loss of Polycomb-associated DNA looping. Together, these results suggest PRC2 uses RNA binding to enhance long-range chromosome folding and H3K27me3 spreading. Developmental gene loci have unique roles in Polycomb spreading, emerging as important architectural elements of the epigenome.
| S-EPMC9295753 | biostudies-literature
Project description:In multicellular organisms, transcription regulation is one of the central mechanisms modelling lineage differentiation and cell-fate determination. Transcription requires dynamic chromatin configurations between promoters and their corresponding distal regulatory elements. It is believed that their communication occurs within large discrete foci of aggregated RNA polymerases termed transcription factories in three-dimensional nuclear space. However, the dynamic nature of chromatin connectivity has not been characterized at the genome-wide level. Here, through a chromatin interaction analysis with paired-end tagging approach using an antibody that primarily recognizes the pre-initiation complexes of RNA polymerase II, we explore the transcriptional interactomes of three mouse cells of progressive lineage commitment, including pluripotent embryonic stem cells, neural stem cells and neurosphere stem/progenitor cells. Our global chromatin connectivity maps reveal approximately 40,000 long-range interactions, suggest precise enhancer-promoter associations and delineate cell-type-specific chromatin structures. Analysis of the complex regulatory repertoire shows that there are extensive colocalizations among promoters and distal-acting enhancers. Most of the enhancers associate with promoters located beyond their nearest active genes, indicating that the linear juxtaposition is not the only guiding principle driving enhancer target selection. Although promoter-enhancer interactions exhibit high cell-type specificity, promoters involved in interactions are found to be generally common and mostly active among different cells. Chromatin connectivity networks reveal that the pivotal genes of reprogramming functions are transcribed within physical proximity to each other in embryonic stem cells, linking chromatin architecture to coordinated gene expression. Our study sets the stage for the full-scale dissection of spatial and temporal genome structures and their roles in orchestrating development.
| S-EPMC3954713 | biostudies-literature
Project description:The genomes of metazoa are organized at multiple scales. Many proteins that regulate genome architecture, including Polycomb group (PcG) proteins, form subnuclear structures. Deciphering mechanistic links between protein organization and chromatin architecture requires precise description and mechanistic perturbations of both. Using super-resolution microscopy, here we show that PcG proteins are organized into hundreds of nanoscale protein clusters. We manipulated PcG clusters by disrupting the polymerization activity of the sterile alpha motif (SAM) of the PcG protein Polyhomeotic (Ph) or by increasing Ph levels. Ph with mutant SAM disrupts clustering of endogenous PcG complexes and chromatin interactions while elevating Ph level increases cluster number and chromatin interactions. These effects can be captured by molecular simulations based on a previously described chromatin polymer model. Both perturbations also alter gene expression. Organization of PcG proteins into small, abundant clusters on chromatin through Ph SAM polymerization activity may shape genome architecture through chromatin interactions.
| S-EPMC4735512 | biostudies-literature
Project description:Insulator sequences help to organize the genome into discrete functional regions by preventing inappropriate cross-regulation. This is thought to be mediated in part through associations with other insulators located elsewhere in the genome. Enhancers that normally drive Drosophila even skipped (eve) expression are located closer to the TER94 transcription start site than to that of eve. We discovered that the region between these genes has enhancer-blocking activity, and that this insulator region also mediates homing of P-element transgenes to the eve-TER94 genomic neighborhood. Localization of these activities to within 0.6 kb failed to separate them. Importantly, homed transgenic promoters respond to endogenous eve enhancers from great distances, and this long-range communication depends on the homing/insulator region, which we call Homie. We also find that the eve promoter contributes to long-distance communication. However, even the basal hsp70 promoter can communicate with eve enhancers across distances of several megabases, when the communication is mediated by Homie. These studies show that, while Homie blocks enhancer-promoter communication at short range, it facilitates long-range communication between distant genomic regions, possibly by organizing a large chromosomal loop between endogenous and transgenic Homies.
| S-EPMC2730365 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-05-13 | GSE150907 | GEO
Project description:The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.
| S-EPMC10917818 | biostudies-literature