Similar Datasets
Project description:Poised enhancers (PEs) represent a genetically distinct set of distal regulatory elements that control the expression of major developmental genes. Before becoming activated in differentiating cells, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally characterized in embryonic stem cells (ESC), it is currently unknown whether PEs are functionally conserved in vivo. Here, we show that the chromatin and 3D structural features of PEs are conserved among mouse pluripotent cells both in vitro and in vivo. We also uncovered that the interactions between PEs and their target genes are globally controlled by the combined action of Polycomb, Trithorax and architectural proteins. Moreover, distal regulatory sequences located close to developmental genes and displaying the typical genetic (i.e. CpG islands) and chromatin (i.e. high accessibility and H3K27me3 levels) features of PEs are commonly found across vertebrates. These putative PEs show high sequence conservation within specific vertebrate clades, with only a few being evolutionary conserved across all vertebrates. Lastly, by genetically disrupting PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential roles during the induction of major developmental genes in vivo.
| S-EPMC8285398 | biostudies-literature
Project description:Transcriptional and phenotypic robustness during development is believed to require complex regulatory landscapes whereby multiple enhancers redundantly control the expression of major cell identity genes. In contrast, we previously described a limited and genetically distinct set of distal regulatory elements, known as poised enhancers (PEs), that control the induction of genes involved in early brain development in a hierarchical and non-redundant manner. Before becoming activated in neural progenitors, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally identified and subsequently characterized using embryonic stem cells (ESC) as in an in vitro differentiation system, it is currently unknown whether PEs are functionally conserved in vivo. Here, we generate and mine various types of genomic data to conclusively show that the epigenetic and 3D structural features of PEs are conserved among pluripotent cells both in vitro and in vivo. Furthermore, by genetically disrupting evolutionary conserved PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential and non-redundant roles during the induction of major anterior neural genes in vivo.
2020-12-31 | GSE160656 | GEO
Project description:Transcriptional and phenotypic robustness during development is believed to require complex regulatory landscapes whereby multiple enhancers redundantly control the expression of major cell identity genes. In contrast, we previously described a limited and genetically distinct set of distal regulatory elements, known as poised enhancers (PEs), that control the induction of genes involved in early brain development in a hierarchical and non-redundant manner. Before becoming activated in neural progenitors, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally identified and subsequently characterized using embryonic stem cells (ESC) as in an in vitro differentiation system, it is currently unknown whether PEs are functionally conserved in vivo. Here, we generate and mine various types of genomic data to conclusively show that the epigenetic and 3D structural features of PEs are conserved among pluripotent cells both in vitro and in vivo. Furthermore, by genetically disrupting evolutionary conserved PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential and non-redundant roles during the induction of major anterior neural genes in vivo.
2020-12-31 | GSE160654 | GEO
Project description:Transcriptional and phenotypic robustness during development is believed to require complex regulatory landscapes whereby multiple enhancers redundantly control the expression of major cell identity genes. In contrast, we previously described a limited and genetically distinct set of distal regulatory elements, known as poised enhancers (PEs), that control the induction of genes involved in early brain development in a hierarchical and non-redundant manner. Before becoming activated in neural progenitors, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally identified and subsequently characterized using embryonic stem cells (ESC) as in an in vitro differentiation system, it is currently unknown whether PEs are functionally conserved in vivo. Here, we generate and mine various types of genomic data to conclusively show that the epigenetic and 3D structural features of PEs are conserved among pluripotent cells both in vitro and in vivo. Furthermore, by genetically disrupting evolutionary conserved PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential and non-redundant roles during the induction of major anterior neural genes in vivo.
2020-12-31 | GSE160653 | GEO
Project description:The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo
| PRJNA673864 | ENA
Project description:The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [HiChIP]
| PRJNA673867 | ENA
Project description:The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [ATAC-seq]
| PRJNA673866 | ENA
Project description:The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [ChIP-seq]
| PRJNA673865 | ENA
Project description:Stem cells of all types are characterized by a stable, heritable state permissive of multiple developmental pathways. The past five years have seen remarkable advances in understanding these heritable states and the ways that they are initiated or terminated. Transcription factors that bind directly to DNA and have sufficiency roles have been most easy to investigate and, perhaps for this reason, are most solidly implicated in pluripotency. In addition, large complexes of ATP-dependent chromatin-remodeling and histone-modification enzymes that have specialized functions have also been implicated by genetic studies in initiating and/or maintaining pluripotency or multipotency. Several of these ATP-dependent remodeling complexes play non-redundant roles, and the esBAF complex facilitates reprogramming of induced pluripotent stem cells. The recent finding that virtually all histone modifications can be rapidly reversed and are often highly dynamic has raised new questions about how histone modifications come to play a role in the steady state of pluripotency. Another surprise from genetic studies has been the frequency with which the global effects of mutations in chromatin regulators can be largely reversed by a single target gene. These genetic studies help define the arena for future mechanistic studies that might be helpful to harness pluripotency for therapeutic goals.
| S-EPMC3085914 | biostudies-literature
Project description:Genomic regions with gene regulatory enhancer activity turnover rapidly across mammals. In contrast, gene expression patterns and transcription factor binding preferences are largely conserved between mammalian species. Based on this conservation, we hypothesized that enhancers active in different mammals would exhibit conserved sequence patterns in spite of their different genomic locations. To investigate this hypothesis, we evaluated the extent to which sequence patterns that are predictive of enhancers in one species are predictive of enhancers in other mammalian species by training and testing two types of machine learning models. We trained support vector machine (SVM) and convolutional neural network (CNN) classifiers to distinguish enhancers defined by histone marks from the genomic background based on DNA sequence patterns in human, macaque, mouse, dog, cow, and opossum. The classifiers accurately identified many adult liver, developing limb, and developing brain enhancers, and the CNNs outperformed the SVMs. Furthermore, classifiers trained in one species and tested in another performed nearly as well as classifiers trained and tested on the same species. We observed similar cross-species conservation when applying the models to human and mouse enhancers validated in transgenic assays. This indicates that many short sequence patterns predictive of enhancers are largely conserved. The sequence patterns most predictive of enhancers in each species matched the binding motifs for a common set of TFs enriched for expression in relevant tissues, supporting the biological relevance of the learned features. Thus, despite the rapid change of active enhancer locations between mammals, cross-species enhancer prediction is often possible. Our results suggest that short sequence patterns encoding enhancer activity have been maintained across more than 180 million years of mammalian evolution.
| S-EPMC6191148 | biostudies-literature