Widespread conservation of chromatin accessibility and transcription factor binding in human and chimpanzee induced pluripotent stem cells
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ABSTRACT:
PROVIDER: PRJNA504642 | ENA |
REPOSITORIES: ENA
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Project description:Changes in gene regulation have been shown to contribute to phenotypic differences between closely related species, most notably in primates. It is likely that a subset of inter-species regulatory differences can be explained by changes in chromatin accessibility and transcription factor binding, yet there is a paucity of comparative data sets with which to investigate this. Using ATAC-seq, we profiled genome-wide chromatin accessibility in a matched set of 6 human and 6 chimpanzee (Pan troglodytes, our closest living relative) induced pluripotent stem cells from which we have previously collected gene expression data. We examined chromatin accessibility patterns near 20,745 orthologous transcriptions start sites and used a footprinting algorithm to predict transcription factor binding activity in each species. We found that the majority of chromatin accessibility patterns and transcription factor activity are conserved between these two closely related species. Interestingly, interspecies divergence in chromatin accessibility and transcription factor binding in pluripotent cells appear to contribute not to differences in the pluripotent state, but to downstream developmental processes. Put together, our findings suggest that the pluripotent state is extremely stable and potentially subject to stronger evolutionary constraint than other somatic tissues.
2018-11-09 | GSE122319 | GEO
Project description:Here we derive human and chimpanzee cranial neural crest cells (CNCCs) and profile histone modifications, transcription factors, chromatin accessibility and gene expression to systematically and quantitatively annotate evolutionary divergence of craniofacial cis-regulatory landscapes. Histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K27me3), chromatin modifiers (p300), transcription factors (NR2F1, TFAP2A), chromatin accessibility (ATACseq) and gene expression (RNAseq) were assayed in CNCCs derived from iPSCs/ESCs from 2 chimpanzee and 3 human individuals.
2015-09-11 | E-GEOD-70751 | biostudies-arrayexpress
Project description:The exit from pluripotency or pluripotent-somatic transition (PST) landmarks an event of mammalian development, and is also a representative cell-fate transition model, but remains largely unresolved. Recently, we reported construction of robust JUN-induced PST completed in one cell cycle and whose dominant regulator SS18/BAFs (Brg1/Brahma-associated factors). However, the transition process in the chromatin architecture and the roles played by BAF are still unknown. Here we report the dynamic changes of chromatin accessibility during JUN-induced PST. Meanwhile, SS18/BAFs mediates PST process by relocating from pluripotent loci to AP-1 associated ones and once compromised, JUN fails to open chromatin and PST will be delayed. Furthermore, we show that the relocation of SS18/BAF partially relays on histone modification H3K27ac, instead of JUN-centric protein-protein interaction. These results reveal the orchestration of master transcription factor, epigenetic machine, and histone modification in the cell fate transition.
2021-10-22 | PXD029277 | iProX
Project description:Gene expression study of human and Chimpanzee iPS cell.
2014-10-31 | GSE62572 | GEO
Project description:ANP32E Restricts Widespread Chromatin Accessibility Through Regulation of H2A.Z
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Project description:Gene expression study of human and Chimpanzee iPS cell. Affymetrix GeneChip Human Genome U133 Plus 2.0 Array were used to examine differentially expressed genes between human and chimpanzee iPS cells
2014-10-31 | E-GEOD-62572 | biostudies-arrayexpress
Project description:Although gene expression divergence has long been postulated to be the primary driver of human evolution, identifying the genes and genetic variants underlying uniquely human traits has proven to be quite challenging. Theory suggests that cell type-specific cis-regulatory variants may fuel evolutionary adaptation due to the specificity of their effects. These variants can precisely tune the expression of a single gene in a single cell type, avoiding the potentially deleterious consequences of trans-acting changes and non-cell type-specific changes that can impact many genes and cell types, respectively. It has recently become possible to quantify human-specific cis-acting regulatory divergence by measuring allele-specific expression in human-chimpanzee hybrid cells—the product of fusing induced pluripotent stem (iPS) cells of each species in vitro. However, these cis-regulatory changes have only been explored in a limited number of tissues and cell types. Here, we quantify human-chimpanzee cis-regulatory divergence in gene expression and chromatin accessibility across six cell types, enabling the identification of highly cell type-specific cis-regulatory changes. We find that cell type-specific genes and regulatory elements evolve faster than those shared across cell types. Furthermore, we identify several instances of lineage-specific natural selection that may have played key roles in specific cell types, such as coordinated changes in the cis-regulation of dozens of genes involved in neuronal firing in motor neurons. Finally, using novel metrics and a machine learning model, we identify genetic variants that likely alter chromatin accessibility and transcription factor binding, leading to neuron-specific changes in the expression of the neurodevelopmentally important genes FABP7 and GAD1. Overall, our results demonstrate that integrative analysis of cis-regulatory divergence in chromatin accessibility and gene expression across cell types is a promising approach to identify the specific genes and genetic variants that make us human.
2023-05-23 | GSE232947 | GEO
Project description:Although gene expression divergence has long been postulated to be the primary driver of human evolution, identifying the genes and genetic variants underlying uniquely human traits has proven to be quite challenging. Theory suggests that cell type-specific cis-regulatory variants may fuel evolutionary adaptation due to the specificity of their effects. These variants can precisely tune the expression of a single gene in a single cell type, avoiding the potentially deleterious consequences of trans-acting changes and non-cell type-specific changes that can impact many genes and cell types, respectively. It has recently become possible to quantify human-specific cis-acting regulatory divergence by measuring allele-specific expression in human-chimpanzee hybrid cells—the product of fusing induced pluripotent stem (iPS) cells of each species in vitro. However, these cis-regulatory changes have only been explored in a limited number of tissues and cell types. Here, we quantify human-chimpanzee cis-regulatory divergence in gene expression and chromatin accessibility across six cell types, enabling the identification of highly cell type-specific cis-regulatory changes. We find that cell type-specific genes and regulatory elements evolve faster than those shared across cell types. Furthermore, we identify several instances of lineage-specific natural selection that may have played key roles in specific cell types, such as coordinated changes in the cis-regulation of dozens of genes involved in neuronal firing in motor neurons. Finally, using novel metrics and a machine learning model, we identify genetic variants that likely alter chromatin accessibility and transcription factor binding, leading to neuron-specific changes in the expression of the neurodevelopmentally important genes FABP7 and GAD1. Overall, our results demonstrate that integrative analysis of cis-regulatory divergence in chromatin accessibility and gene expression across cell types is a promising approach to identify the specific genes and genetic variants that make us human.
2023-05-23 | GSE232948 | GEO
Project description:Single cell ATAC-seq (scATAC-seq) was performed at various stages of differentiation of chimpanzee induced pluripotent stem cells (iPSC) to 4 month old cerebral organoids. scATAC-seq was performed on the following days of differentiation: day 0 (pluripotent stem cell), day 4 (embryoid body), day 10 (neuroectoderm), day 15 (neuroepithelium), day 30 (1 month old cerebral organoid), day 60 (2 months old cerebral organoid), and day 120 (4 months old cerebral organoid).
2019-10-16 | E-MTAB-8043 | biostudies-arrayexpress
Project description:Here we derive human and chimpanzee cranial neural crest cells (CNCCs) and profile histone modifications, transcription factors, chromatin accessibility and gene expression to systematically and quantitatively annotate evolutionary divergence of craniofacial cis-regulatory landscapes.
2015-09-11 | GSE70751 | GEO