Promoter-enhancer communication occurs primarily within Gene Unit Sub-TADs (GUSTs)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA474608 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7262950.fastq.gz | Fastqsanger.gz | |||
| SRR7262960.fastq.gz | Fastqsanger.gz | |||
| SRR7262970.fastq.gz | Fastqsanger.gz | |||
| SRR7262980.fastq.gz | Fastqsanger.gz | |||
| SRR7262990.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 60 |
Similar Datasets
Project description:The mammalian genome is sequentially partitioned from chromosomes into looped chromatin regions termed Topologically Associating Domains (TADs), and then into numerous smaller sub-TAD loops, each bounded and insulated by CTCF and Cohesin. The sub-TADs encompass enhancers, promoters and often multiple genes but whether promoter-enhancer interactions and gene regulation are broadly restricted to within the sub-TAD loops has not been functionally determined. Here we identify “Gene Unit Sub-TADs” or GUSTs as a class of sub-TADs that confine promoter-enhancer interactions and demarcate functional gene regulatory regions. We depleted Estrogen-related receptor β (Esrrb), which binds to the Mediator co-activator complex, to impair the activity of enhancers controlling 245 mouse embryonic stem cell genes. We find that most Esrrb-responsive enhancers lack significant Cohesin binding but instead correlate with Mediator binding. Esrrb depletion causes reduced Mediator binding, decreased nascent RNA expression and diminished promoter-enhancer looping. In 88% of the cases examined, the effects of Esrrb depletion are restricted to enhancers and target genes within GUSTs. In some GUSTs, active genes lay alongside inactive ones but are distinguished by their proximal promoter chromatin accessibility, explaining further the specificity of enhancer-promoter interactions within GUSTs. Our data indicate that GUSTs represent functional gene regulons in mammalian genomes.
2018-10-19 | GSE115340 | GEO
Project description:Metazoan chromosomes are sequentially partitioned into topologically associating domains (TADs) and then into smaller sub-domains. One class of sub-domains, insulated neighborhoods, are proposed to spatially sequester and insulate the enclosed genes through self-association and chromatin looping. However, it has not been determined functionally whether promoter-enhancer interactions and gene regulation are broadly restricted to within these loops. Here, we employed published datasets from murine embryonic stem cells (mESCs) to identify insulated neighborhoods that confine promoter-enhancer interactions and demarcate gene regulatory regions. To directly address the functionality of these regions, we depleted estrogen-related receptor β (Esrrb), which binds the Mediator co-activator complex, to impair enhancers of genes within 222 insulated neighborhoods without causing mESC differentiation. Esrrb depletion reduces Mediator binding, promoter-enhancer looping, and expression of both nascent RNA and mRNA within the insulated neighborhoods without significantly affecting the flanking genes. Our data indicate that insulated neighborhoods represent functional regulons in mammalian genomes.
| S-EPMC6338517 | biostudies-literature
Project description:Primarily cultured neurospheres
| PRJNA599138 | ENA
Project description:HoxA genes exhibit central roles during development and causal mutations have been found in several human syndromes including limb malformation. Despite their importance, information on how these genes are regulated is lacking. Here, we report on the first identification of bona fide transcriptional enhancers controlling HoxA genes in developing limbs and show that these enhancers are grouped into distinct topological domains at the sub-megabase scale (sub-TADs). We provide evidence that target genes and regulatory elements physically interact with each other through contacts between sub-TADs rather than by the formation of discreet "DNA loops". Interestingly, there is no obvious relationship between the functional domains of the enhancers within the limb and how they are partitioned among the topological domains, suggesting that sub-TAD formation does not rely on enhancer activity. Moreover, we show that suppressing the transcriptional activity of enhancers does not abrogate their contacts with HoxA genes. Based on these data, we propose a model whereby chromatin architecture defines the functional landscapes of enhancers. From an evolutionary standpoint, our data points to the convergent evolution of HoxA and HoxD regulation in the fin-to-limb transition, one of the major morphological innovations in Vertebrates. The chromatin binding of the RNA polymerase II and the sub-unit Med12 of the Mediator complexe were analysed by ChIP-sequencing mouse distal E11.5 forelimb. This approach allowed us to identify the position of limb-specific enhancers.
2013-11-19 | E-GEOD-52483 | biostudies-arrayexpress
Project description:Understanding how genomes encode complex cellular and organismal behaviors is an outstanding challenge of modern genetics. Unlike classical screening methods, analysis of the genetic variation that occurs naturally in wild populations can enable rapid, genome-scale trait mapping with a medium-throughput experimental design. Here we describe the results of the first genome-wide association analysis (GWAS) of a microbial eukaryote, using wild isolates of the filamentous fungus Neurospora crassa. We transcriptionally profiled each of 112 individuals collected in Louisiana and used RNA-seq data to genotype each strain at thousands of genetic loci genome-wide. We used these genotypes in a mapping analysis of microbial communication. In N. crassa, germinated asexual spores (germlings) sense the presence of other germlings, grow toward them in a coordinated fashion, and fuse. We evaluated germlings of each strain for their ability to chemically sense, chemotropically seek, and undergo cell fusion. GWAS identified one gene, NCU04379 (cse-1, encoding a homolog of neuronal calcium sensor), at which inheritance was strongly associated with the efficiency of germling communication. Deletion of cse-1 significantly lowered germling communication and fusion, and two genes encoding predicted binding partners of CSE-1 were also required for the communication trait. Additionally, mining our association results for signaling and secretion genes with a potential role in germling communication, we validated six more novel determinants of germling communication, including a secreted protease and two other genes whose deletion conferred a novel phenotype of increased communication and multi-germling fusion. These results establish protein secretion as a linchpin of germling communication in N. crassa and shed light on the regulation of communication molecules in this fungus. Our study demonstrates the power of population-genetic analyses for the rapid identification of genes contributing to complex traits in microbial species. 112 mycelial mRNA profiles of 16 hour wild type (WT) Neurospora crassa strains were generated by deep sequencing, using Illumina GAIIx.
2013-03-28 | E-GEOD-45406 | biostudies-arrayexpress
Project description:Paternal genomes are compacted during spermiogenesis and de-compacted following fertilization. These processes are fundamental for inheritance but incompletely understood. We analyzed these processes in the frog Xenopus laevis, whose sperm can be assembled into functional pronuclei in egg extracts in vitro. In such extracts, cohesin extrudes DNA into loops, but in vivo cohesin only assembles topologically-associating domains (TADs) at the mid-blastula transition (MBT). Why cohesin assembles TADs only at this stage is unknown. We first analyzed genome architecture in frog sperm and compared it to human and mouse. Our results indicate that sperm genome organization is conserved between frogs and humans and occurs without formation of TADs. TADs can be detected in mouse sperm samples, as reported, but these structures might originate from somatic chromatin contaminations. We therefore discuss the possibility that the absence of TADs might be a general feature of vertebrate sperm. To analyze sperm genome remodeling upon fertilization, we reconstituted male pronuclei in Xenopus egg extracts. In pronuclei, chromatin compartmentalization increases but cohesin does not accumulate at CTCF sites and assemble TADs. However, if pronuclei are formed in the presence of exogenous CTCF, CTCF binds to its consensus sites, cohesin accumulates at these and forms short-range chromatin loops, which are preferentially anchored at CTCF’s N-terminus. These results indicate that TADs are only assembled at MBT because before this stage CTCF sites are not occupied and cohesin only forms short-range chromatin loops.
2023-10-25 | GSE237050 | GEO
Project description:Paternal genomes are compacted during spermiogenesis and de-compacted following fertilization. These processes are fundamental for inheritance but incompletely understood. We analyzed these processes in the frog Xenopus laevis, whose sperm can be assembled into functional pronuclei in egg extracts in vitro. In such extracts, cohesin extrudes DNA into loops, but in vivo cohesin only assembles topologically-associating domains (TADs) at the mid-blastula transition (MBT). Why cohesin assembles TADs only at this stage is unknown. We first analyzed genome architecture in frog sperm and compared it to human and mouse. Our results indicate that sperm genome organization is conserved between frogs and humans and occurs without formation of TADs. TADs can be detected in mouse sperm samples, as reported, but these structures might originate from somatic chromatin contaminations. We therefore discuss the possibility that the absence of TADs might be a general feature of vertebrate sperm. To analyze sperm genome remodeling upon fertilization, we reconstituted male pronuclei in Xenopus egg extracts. In pronuclei, chromatin compartmentalization increases but cohesin does not accumulate at CTCF sites and assemble TADs. However, if pronuclei are formed in the presence of exogenous CTCF, CTCF binds to its consensus sites, cohesin accumulates at these and forms short-range chromatin loops, which are preferentially anchored at CTCF’s N-terminus. These results indicate that TADs are only assembled at MBT because before this stage CTCF sites are not occupied and cohesin only forms short-range chromatin loops.
2023-10-25 | GSE237049 | GEO
Project description:Virus-induced apoptosis in human cerebral organoids occurs primarily in committed neurons and is associated with a limited interferon stimulated gene response
| PRJNA543536 | ENA
Project description:Understanding how genomes encode complex cellular and organismal behaviors is an outstanding challenge of modern genetics. Unlike classical screening methods, analysis of the genetic variation that occurs naturally in wild populations can enable rapid, genome-scale trait mapping with a medium-throughput experimental design. Here we describe the results of the first genome-wide association analysis (GWAS) of a microbial eukaryote, using wild isolates of the filamentous fungus Neurospora crassa. We transcriptionally profiled each of 112 individuals collected in Louisiana and used RNA-seq data to genotype each strain at thousands of genetic loci genome-wide. We used these genotypes in a mapping analysis of microbial communication. In N. crassa, germinated asexual spores (germlings) sense the presence of other germlings, grow toward them in a coordinated fashion, and fuse. We evaluated germlings of each strain for their ability to chemically sense, chemotropically seek, and undergo cell fusion. GWAS identified one gene, NCU04379 (cse-1, encoding a homolog of neuronal calcium sensor), at which inheritance was strongly associated with the efficiency of germling communication. Deletion of cse-1 significantly lowered germling communication and fusion, and two genes encoding predicted binding partners of CSE-1 were also required for the communication trait. Additionally, mining our association results for signaling and secretion genes with a potential role in germling communication, we validated six more novel determinants of germling communication, including a secreted protease and two other genes whose deletion conferred a novel phenotype of increased communication and multi-germling fusion. These results establish protein secretion as a linchpin of germling communication in N. crassa and shed light on the regulation of communication molecules in this fungus. Our study demonstrates the power of population-genetic analyses for the rapid identification of genes contributing to complex traits in microbial species.
2013-03-28 | GSE45406 | GEO