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Identification of DNA methylation differences correlated with transcriptional divergence between humans and chimpanzees in chromosomes 21 and 22

ABSTRACT: Identification of DNA methylation differences correlated with transcriptional divergence between humans and chimpanzees in chromosomes 21 and 22

PROVIDER: PRJNA152359 | ENA |

REPOSITORIES: ENA

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Identification of DNA methylation differences correlated with transcriptional divergence between humans and chimpanzees in chromosomes 21 and 22

Project description:While some studies have reported gene expression differences between humans and chimpanzees, the mechanisms underlying such changes remain poorly understood. To address this issue, we examined, by MeDIP-chip, DNA methylation patterns of peripheral blood cells from age- and sex- matched human and chimpanzee individuals. Our analysis identified some differentially methylated regions between the two species and suggests that changes in DNA methylation pattern are involved in the diversification of transcriptome during evolution.

2012-02-02 | GSE35475 | GEO

Age-Associated Epigenetic Change in Chimpanzees and Humans

Project description:Genome wide DNA methylation profiling of captive chimpanzees of ages spanning the chimpanzee lifespan (whole blood) Methylation levels have been shown to change with age at sites across the human genome. Change at some of these sites is so consistent across individuals that it can be used as an “epigenetic clock” to predict an individual’s chronological age within a few years. Studies of age-related epigenetic change in other mammals, including mice, whales, and canids, show that some but not all of the same loci as in humans undergo age-associated methylation changes. An in-depth comparison of chimpanzees with humans is of interest because the two species are genetically similar but differ in lifespan. To this end, we profiled genome-wide blood methylation levels for 113 samples from 83 chimpanzees aged 1-58 years (26 chimpanzees were sampled at multiple ages during their lifespan). We used this data to build a chimpanzee-specific epigenetic clock model as well as to compare genome-wide patterns of change with age between humans and chimpanzees more generally.

2020-08-23 | GSE136296 | GEO

Divergence in alternative polyadenylation between humans and chimpanzees contributes to gene regulatory differences between species

Project description:Differences in gene regulation contribute to phenotypic differences between humans and other primates. While co-transcriptional gene regulatory mechanisms such as alternative polyadenylation (APA) can help explain how variation in gene regulation manifests, such mechanisms remain understudied. We measured polyadenylation site (PAS) usage in a panel of 6 human and 6 chimpanzee lymphoblastoid cell lines (LCLs). While APA is largely conserved between humans and chimpanzees, genes with divergent APA patterns are enriched among differentially expressed and differentially translated genes. Differential usage of 3’ UTR and intronic PAS are both significantly correlated with differential mRNA expression effect sizes but in opposite directions. For many genes, there is one PAS dominant, meaning it is used much more often than others. The dominant PAS for these gene is overwhelmingly shared between species, however, differences in dominant PAS are enriched for genes with expression differences. Finally, through post-translational mechanisms, we believe APA contributes to genes differentially expressed at the protein level but not in mRNA. As this is the first primate comparative study of APA, our study establishes APA as a key mechanism underlying the genetic regulation of gene and protein expression levels in primates.

2021-01-22 | GSE155245 | GEO

Divergence in alternative polyadenylation between humans and chimpanzees contributes to gene regulatory differences between species

Project description:Divergence in alternative polyadenylation between humans and chimpanzees contributes to gene regulatory differences between species

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Epigenetic aging of the prefrontal cortex and cerebellum in humans, chimpanzees, and rhesus macaques

Project description:Genome-wide prefrontal cortex and cerebellum DNA methylation profiles of younger and older adult humans, captive chimpanzees, and captive rhesus macaques

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Transcription profiling of brain in three adult humans and three adult chimpanzees

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A generally conserved response to hypoxia in iPSC-derived cardiomyocytes from humans and chimpanzees

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Genetic studies of human-chimpanzee divergence using stem cell fusions

Project description:Complete genome sequencing has identified millions of DNA changes that differ between humans and chimpanzees. Although a subset of these changes likely underlies important phenotypic differences between humans and chimpanzees, it is currently difficult to distinguish causal from incidental changes and to map specific phenotypes to particular genome locations. To facilitate further genetic study of human-chimpanzee divergence, we have generated human and chimpanzee auto-tetraploids and allo-tetraploids by fusing induced pluripotent stem cells (iPSCs) of each species. The resulting tetraploid iPSCs can be stably maintained and retain the ability to differentiate along ectoderm, mesoderm, and endoderm lineages. RNA sequencing identifies thousands of genes whose expression differs between humans and chimpanzees when assessed in single-species diploid or auto-tetraploid iPSCs. Analysis of gene expression patterns in inter-specific allo-tetraploid iPSCs shows that human-chimpanzee expression differences arise from substantial contributions of both cis-acting changes linked to the genes themselves, and trans-acting changes elsewhere in the genome. To enable further genetic mapping of species differences, we tested chemical treatments for stimulating genome-wide mitotic recombination between human and chimpanzee chromosomes, and CRISPR methods for inducing species-specific changes on particular chromosomes in allo-tetraploid cells. We successfully generated derivative cells with nested deletions or inter-specific recombination on the X chromosome. These studies identify a long distance cis-regulatory domain of the Fragile X-associated gene (FMR1), confirm an important role for the X chromosome in trans-regulation of other expression differences, and illustrate the potential of this system for more detailed mapping of the molecular basis of human and chimpanzee evolution.

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Project description:We used embryoid bodies to compare differences in gene expression between humans and chimpanzees in a large number of cell types

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Project description:Age-Associated Epigenetic Change in Chimpanzees and Humans

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