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Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [Dnase-seq]

ABSTRACT: Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [Dnase-seq]

PROVIDER: PRJNA238021 | ENA |

REPOSITORIES: ENA

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Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [Dnase-seq]

Project description:The human genome shares a remarkable amount of genomic sequence with our closest living primate relatives. Researchers have long sought to understand what regions of the genome are responsible for unique species-specific traits. Previous studies have shown that many genes are differentially expressed between species, but the regulatory elements contributing to these differences are largely unknown. Here we report a genome-wide comparison of active gene regulatory elements in human, chimpanzee, and macaque, and we identify hundreds of regulatory elements that have been gained or lost in the human or chimpanzee genomes since their evolutionary divergence. These elements contain evidence of natural selection and correlate with species-specific changes in gene expression. Polymorphic DNA bases in transcription factor motifs that we found in these regulatory elements may be responsible for the varied biological functions across species. This study directly links phenotypic and transcriptional differences between species with changes in chromatin structure. One biological replicate was analyzed for each of the 15 primate samples using DNase-seq.

2014-02-13 | E-GEOD-54907 | biostudies-arrayexpress

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [DGE-seq]

Project description:Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [DGE-seq]

| PRJNA238022 | ENA

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [Dnase-seq]

2014-02-13 | GSE54907 | GEO

Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

Project description:Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species.

| S-EPMC3386175 | biostudies-literature

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-02-13 | E-GEOD-54908 | biostudies-arrayexpress

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-02-13 | GSE54908 | GEO

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [DGE-seq]

2014-02-13 | E-GEOD-54906 | biostudies-arrayexpress

Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [DGE-seq]

2014-02-13 | GSE54906 | GEO

Epigenetic features of differentiation-regulated replication origins

Project description:To identify chromatin states and histone modifications that locally mark replication origins, we profiled origin distributions in eight human cell lines representing embryonic and differentiated cell types. Consistent with a role for chromatin in determining origin activity, we found that cancer and non-cancer cells of similar lineages exhibited highly similar replication origin distributions. Surprisingly, our study revealed that DNAse hypersensitivity, which often correlates with early replication at large-scale chromatin domains, did not emerge as a strong local determinant of origin activity. Instead, we found that two distinct sets of chromatin modifications exhibited strong local associations with two discrete groups of replication origins. The first origin group consisted of about 50,000 regions that actively initiated replication in all cell types examined and preferentially colocalized with unmethylated CpGs and with the euchromatin markers, H3K4me3 and H3K9Ac. The second group consisted of origins that were consistently active in cells of a single type or lineage and preferentially colocalized with the heterochromatin marker, H3K9me3. Shared origins replicated throughout the S-phase of the cell cycle, whereas cell-type specific origins preferentially replicated during late S-phase.

2016-05-11 | GSE80391 | GEO

SMARCA4 Rescue Profiling [Dnase]

Project description:SMARCA4 Rescue Profiling [Dnase]

| PRJNA547550 | ENA