ChIP-chip from human fetal brain with H3K27Ac and H3K4Me1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE57354 | GEO | 2015/01/30
SECONDARY ACCESSION(S): PRJNA247499
REPOSITORIES: GEO
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Project description:Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. We tested this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved non-coding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with the linkage score. We tested more than 1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene, with a focus on genes involved in X-linked intellectual disabilities (ID). The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer's function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression. ChIP-chip from human fetal brain using H3K27Ac or H3K4Me1 antibodies. Biological replicates: H3K27Ac_Rep1, H3K27Ac_Rep2 Biological replicates: H3K4Me1_Rep1, H3K4Me1_Rep2
2015-01-30 | E-GEOD-57354 | biostudies-arrayexpress
Project description:Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. We tested this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved non-coding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with the linkage score. We tested more than 1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene, with a focus on genes involved in X-linked intellectual disabilities (ID). The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer's function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression. ChIP-chip from mouse 14.5 days fetal brain using P300 or H3K4Me1 antibodies. Biological replicates: P300_Rep1, P300_Rep2 Biological replicates: H3K4Me1_Rep1,H3K4Me1_Rep2
2015-01-30 | E-GEOD-57357 | biostudies-arrayexpress
Project description:Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. We tested this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved non-coding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with the linkage score. We tested more than 1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene, with a focus on genes involved in X-linked intellectual disabilities (ID). The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer's function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression.
2015-01-30 | GSE57357 | GEO
Project description:The vertebrate body plan and organs are shaped during a highly conserved embryonic phase called the phylotypic stage, however the mechanisms that guide the epigenome through this transition and their evolutionary conservation remain elusive. Here we report widespread DNA demethylation of thousands of enhancers during the phylotypic period in zebrafish, Xenopus and mouse. These dynamic enhancers are linked to essential developmental genes that display coordinated transcriptional and epigenomic changes in the diverse vertebrates during embryogenesis. Phylotypic stage-specific binding of Tet proteins to (hydroxy)methylated DNA, and enrichment of hydroxymethylcytosine on these enhancers, implicated active DNA demethylation in this process. Furthermore, loss of function of Tet1/2/3 in zebrafish caused reduced chromatin accessibility and increased methylation levels specifically on these enhancers, indicative of DNA methylation being an upstream regulator of phylotypic enhancer function. Overall, our study reveals a novel regulatory module associated with the most conserved phase of vertebrate embryogenesis and uncovers an ancient developmental role for the Tet dioxygenases.
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2020-11-02 | GSE160588 | GEO
Project description:Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Yet, information on physiological roles and underlying signaling mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with a novel multiple congenital anomaly disorder caused by hemizygous variants in OTUD5, encoding a K48-/K63-linkage-specific deubiquitylase. By studying these mutations, we find that OTUD5 controls neuroectodermal differentiation through cleaving K48-linked ubiquitin chains to counteract degradation of a select group of chromatin regulators. These include ARID1A/B, HDAC2, and HCF1, mutation of which underlie different developmental disorders that exhibit phenotypic overlap with OTUD5 patients. Consequently, loss of OTUD5 during early differentiation leads to less accessible chromatin at neuroectodermal enhancers and thus aberrant rewiring of gene expression networks. Our study describes a novel developmental disorder we name LINKED (LINKage-specific-deubiquitylation-deficiency-induced Embryonic Defects) syndrome, provides a previously unrecognized mechanistic link between phenotypically related diseases, and reveals linkage-specific ubiquitin cleavage from substrate groups (i.e. chromatin remodelers) as an essential mode of signaling required to coordinate embryonic differentiation pathways.
2020-11-02 | GSE160589 | GEO
Project description:The corneal epithelium is a stratified squamous epithelium that protects the eye from mechanical and toxic stress. In this system, cells are continually being sloughed off from the surface of the eye, and replenished by proliferation from corneal stem cells in the limbus, which migrate in and differentiate. During tissue development and homeostasis, distal regulatory regions called enhancers, which contain binding sites for numerous transcription factors, help to control and coordinate gene expression in a temporal and spatial specific manner. To identify enhancers in cornea epithelia, we performed ChIP-Seq with antibodies to the histone marks H3K4me3, H3K4me1, and H3K27ac in primary human corneal epithelial cells. Active enhancers were defined as having high levels of H3K4me1 and H3K27ac, and low levels of H3K4me3: 12,900 such regions were identified in the corneal epithelial cells. In combination with primary cell histone modification ChIP-Seq data from BROAD, 2946 active enhancer regions were identified that are unique to the corneal epithelial cells: 1551 of theses 2946 also overlie regions of high evolutionary constraint. Motif enrichment analysis of these regions has revealed binding sites for a number of transcription factors, highlighting their roles as key regulators of corneal epithelial development.
2017-06-01 | GSE43499 | GEO
Project description:Despite deep evolutionary conservation, recombination varies greatly across the genome, among individuals, sexes and populations and can be a major evolutionary force in the wild. Yet this variation in recombination and its impact on adaptively diverging populations is not well understood. To elucidate the nature and potential consequences of recombination rate variation, we characterized fine-scale recombination landscapes by combining pedigrees, functional genomics and field fitness measurements in an adaptively divergent pair of marine and freshwater threespine stickleback populations from River Tyne, Scotland. Through whole-genome sequencing of large nuclear families, we identified the genomic location of almost 50,000 crossovers and built recombination maps for 36 marine, freshwater, and hybrid individuals at 3.8 kilobase resolution. Using these maps, we quantified the factors driving variation in recombination rate: we find strong heterochiasmy between sexes (68% of the variation) but also differences among ecotypes (21.8%). Hybrids show evidence of significant recombination suppression, both in overall map length and in individual loci. We further tested and found reduced recombination rates both within single marine–freshwater adaptive loci and between loci on the same chromosome, suggestive of selection on linked ‘cassettes’. We tested theory supporting the evolution of linked selection using temporal sampling along a natural hybrid zone, and found that recombinants with shuffled alleles across loci show traits associated with reduced fitness. Our results support predictions that divergence in cis-acting recombination modifiers whose mechanisms are disrupted in hybrids, may have an important role to play in the maintenance of differences among adaptively diverging populations.
2024-05-24 | GSE254557 | GEO
Project description:Despite deep evolutionary conservation, recombination varies greatly across the genome, among individuals, sexes and populations and can be a major evolutionary force in the wild. Yet this variation in recombination and its impact on adaptively diverging populations is not well understood. To elucidate the nature and potential consequences of recombination rate variation, we characterized fine-scale recombination landscapes by combining pedigrees, functional genomics and field fitness measurements in an adaptively divergent pair of marine and freshwater threespine stickleback populations from River Tyne, Scotland. Through whole-genome sequencing of large nuclear families, we identified the genomic location of almost 50,000 crossovers and built recombination maps for 36 marine, freshwater, and hybrid individuals at 3.8 kilobase resolution. Using these maps, we quantified the factors driving variation in recombination rate: we find strong heterochiasmy between sexes (68% of the variation) but also differences among ecotypes (21.8%). Hybrids show evidence of significant recombination suppression, both in overall map length and in individual loci. We further tested and found reduced recombination rates both within single marine–freshwater adaptive loci and between loci on the same chromosome, suggestive of selection on linked ‘cassettes’. We tested theory supporting the evolution of linked selection using temporal sampling along a natural hybrid zone, and found that recombinants with shuffled alleles across loci show traits associated with reduced fitness. Our results support predictions that divergence in cis-acting recombination modifiers whose mechanisms are disrupted in hybrids, may have an important role to play in the maintenance of differences among adaptively diverging populations.
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