Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long-range genomic interactions epigenetically regulate the expression of a cytokine receptor.

ABSTRACT: Current research on the cytokine-mediated signalling towards the polarization and differentiation of a T-helper cell lineage lacks mechanistic insights on the transcriptional regulation of cytokine receptor genes. Here, we propose a new mechanism for the transcriptional regulation of the interferon gamma receptor 1 gene via long-range intrachromosomal interactions with the Ifn? locus mediated by the protein CTCF. These interactions sustain the monoallelic expression of the differentially methylated Ifn?R1 gene and are persistent on blockade of active transcription. Our findings suggest that regulatory elements for a cytokine gene locus can also positively regulate the transcription of its receptor.

SUBMITTER: Deligianni C

PROVIDER: S-EPMC3432804 | biostudies-other | 2012 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Long-range genomic interactions epigenetically regulate the expression of a cytokine receptor.

Deligianni Chrysoula C Spilianakis Charalampos G CG

EMBO reports 20120727 9

Current research on the cytokine-mediated signalling towards the polarization and differentiation of a T-helper cell lineage lacks mechanistic insights on the transcriptional regulation of cytokine receptor genes. Here, we propose a new mechanism for the transcriptional regulation of the interferon gamma receptor 1 gene via long-range intrachromosomal interactions with the Ifnγ locus mediated by the protein CTCF. These interactions sustain the monoallelic expression of the differentially methyla ...[more]

PMID: 22836578

Similar Datasets

Long-range chromosomal interactions regulate the timing of the transition between poised and active gene expression.

Project description:To understand how mammalian genes are regulated from their natural chromosomal environment, we have analysed the molecular events occurring throughout a 150 kb chromatin segment containing the alpha globin gene locus as it changes from a poised, silent state in erythroid progenitors, to the fully activated state in late, erythroid cells. Active transcription requires the late recruitment of general transcription factors, mediator and Pol II not only to the promoter but also to its remote regulatory elements. Natural mutants of the alpha cluster show that whereas recruitment of the pre-initiation complex to the upstream elements occurs independently, recruitment to the promoter is largely dependent on the regulatory elements. An improved, quantitative chromosome conformation capture analysis demonstrates that this recruitment is associated with a conformational change, in vivo, apposing the promoter with its remote regulators, consistent with a chromosome looping mechanism. These findings point to a general mechanism by which a gene can be held in a poised state until the appropriate stage for expression, coordinating the level and timing of gene expression during terminal differentiation.

| S-EPMC1852780 | biostudies-literature

Long range interactions regulate Igf2 gene transcription during skeletal muscle differentiation.

Project description:The differentiation, maintenance, and repair of skeletal muscle is controlled by interactions between genetically determined transcriptional programs regulated by myogenic transcription factors and environmental cues activated by growth factors and hormones. Signaling through the insulin-like growth factor 1 (IGF1) receptor by locally produced IGF2 defines one such pathway that is critical for normal muscle growth and for regeneration after injury. IGF2 gene and protein expression are induced as early events in muscle differentiation, but the responsible molecular mechanisms are unknown. Here we characterize a distal DNA element within the imprinted mouse Igf2-H19 locus with properties of a muscle transcriptional enhancer. We find that this region undergoes a transition to open chromatin during differentiation, whereas adjacent chromatin remains closed, and that it interacts in differentiating muscle nuclei but not in mesenchymal precursor cells with the Igf2 gene found more than 100 kb away, suggesting that chromatin looping or sliding to bring the enhancer in proximity to Igf2 promoters is also an early event in muscle differentiation. Because this element directly stimulates the transcriptional activity of an Igf2 promoter-reporter gene in differentiating myoblasts, our results indicate that we have identified a bona fide distal transcriptional enhancer that supports Igf2 gene activation in skeletal muscle cells. Because this DNA element is conserved in the human IGF2-H19 locus, our results further suggest that its muscle enhancer function also is conserved among different mammalian species.

| S-EPMC2998108 | biostudies-literature

Long-Range Interactions in Riboswitch Control of Gene Expression.

Project description:Riboswitches are widespread RNA motifs that regulate gene expression in response to fluctuating metabolite concentrations. Known primarily from bacteria, riboswitches couple specific ligand binding and changes in RNA structure to mRNA expression in cis. Crystal structures of the ligand binding domains of most of the phylogenetically widespread classes of riboswitches, each specific to a particular metabolite or ion, are now available. Thus, the bound states-one end point-have been thoroughly characterized, but the unbound states have been more elusive. Consequently, it is less clear how the unbound, sensing riboswitch refolds into the ligand binding-induced output state. The ligand recognition mechanisms of riboswitches are diverse, but we find that they share a common structural strategy in positioning their binding sites at the point of the RNA three-dimensional fold where the residues farthest from one another in sequence meet. We review how riboswitch folds adhere to this fundamental strategy and propose future research directions for understanding and harnessing their ability to specifically control gene expression.

| S-EPMC7374767 | biostudies-literature

Long-range chromatin interactions in pathogenic gene expression control.

Project description:A large number of distal cis-regulatory elements (cREs) have been annotated in the human genome, which plays a central role in orchestrating spatiotemporal gene expression. Since many cREs regulate non-adjacent genes, long-range cRE-promoter interactions are an important factor in the functional characterization of the engaged cREs. In this regard, recent studies have demonstrated that identification of long-range target genes can decipher the effect of genetic mutations residing within cREs on abnormal gene expression. In addition, investigation of altered long-range cREs-promoter interactions induced by chromosomal rearrangements has revealed their critical roles in pathogenic gene expression. In this review, we briefly discuss how the analysis of 3D chromatin structure can help us understand the functional impact of cREs harboring disease-associated genetic variants and how chromosomal rearrangements disrupting topologically associating domains can lead to pathogenic gene expression.

| S-EPMC7714423 | biostudies-literature

Variegated gene expression caused by cell-specific long-range DNA interactions.

Project description:Mammalian genomes contain numerous regulatory DNA sites with unknown target genes. We used mice with an extra ?-globin locus control region (LCR) to investigate how a regulator searches the genome for target genes. We find that the LCR samples a restricted nuclear subvolume, wherein it preferentially contacts genes controlled by shared transcription factors. No contacted gene is detectably upregulated except for endogenous ?-globin genes located on another chromosome. This demonstrates genetically that mammalian trans activation is possible, but suggests that it will be rare. Trans activation occurs not pan-cellularly, but in 'jackpot' cells enriched for the interchromosomal interaction. Therefore, cell-specific long-range DNA contacts can cause variegated expression.

| S-EPMC3151580 | biostudies-literature

Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression.

Project description:Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes in vivo. As genome-wide transcription is organized under the high-order chromosome structure, it is largely uncharted how circadian gene expression is influenced by chromosome architecture. We focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm. Using circular chromosome conformation capture sequencing, we systematically examined the interacting loci of a Bmal1-bound super-enhancer upstream of a clock gene Nr1d1 in mouse liver. These interactions are largely stable in the circadian cycle and cohesin binding sites are enriched in the interactome. Global analysis showed that cohesin-CTCF co-binding sites tend to insulate the phases of circadian oscillating genes while cohesin-non-CTCF sites are associated with high circadian rhythmicity of transcription. A model integrating the effects of cohesin and CTCF markedly improved the mechanistic understanding of circadian gene expression. Further experiments in cohesin knockout cells demonstrated that cohesin is required at least in part for driving the circadian gene expression by facilitating the enhancer-promoter looping. This study provided a novel insight into the relationship between circadian transcriptome and the high-order chromosome structure.

| S-EPMC4852938 | biostudies-literature

Effective gene expression prediction from sequence by integrating long-range interactions.

Project description:How noncoding DNA determines gene expression in different cell types is a major unsolved problem, and critical downstream applications in human genetics depend on improved solutions. Here, we report substantially improved gene expression prediction accuracy from DNA sequences through the use of a deep learning architecture, called Enformer, that is able to integrate information from long-range interactions (up to 100 kb away) in the genome. This improvement yielded more accurate variant effect predictions on gene expression for both natural genetic variants and saturation mutagenesis measured by massively parallel reporter assays. Furthermore, Enformer learned to predict enhancer-promoter interactions directly from the DNA sequence competitively with methods that take direct experimental data as input. We expect that these advances will enable more effective fine-mapping of human disease associations and provide a framework to interpret cis-regulatory evolution.

| S-EPMC8490152 | biostudies-literature

Long-range DNA-water interactions.

Project description:DNA functions only in aqueous environments and adopts different conformations depending on the hydration level. The dynamics of hydration water and hydrated DNA leads to rotating and oscillating dipoles that, in turn, give rise to a strong megahertz to terahertz absorption. Investigating the impact of hydration on DNA dynamics and the spectral features of water molecules influenced by DNA, however, is extremely challenging because of the strong absorption of water in the megahertz to terahertz frequency range. In response, we have employed a high-precision megahertz to terahertz dielectric spectrometer, assisted by molecular dynamics simulations, to investigate the dynamics of water molecules within the hydration shells of DNA as well as the collective vibrational motions of hydrated DNA, which are vital to DNA conformation and functionality. Our results reveal that the dynamics of water molecules in a DNA solution is heterogeneous, exhibiting a hierarchy of four distinct relaxation times ranging from ∼8 ps to 1 ns, and the hydration structure of a DNA chain can extend to as far as ∼18 Å from its surface. The low-frequency collective vibrational modes of hydrated DNA have been identified and found to be sensitive to environmental conditions including temperature and hydration level. The results reveal critical information on hydrated DNA dynamics and DNA-water interfaces, which impact the biochemical functions and reactivity of DNA.

| S-EPMC8633837 | biostudies-literature

Glucocorticoid receptor activation of the Ciz1-Lcn2 locus by long range interactions.

Project description:The cellular response to glucocorticoid receptor (GR) activation involves a highly orchestrated series of regulatory actions influenced at multiple levels by a variety of mechanisms including the action of transcription factors and chromatin modifiers. Because the majority of GR binding sites (glucocorticoid-responsive elements (GREs)) are distant from promoters, it is likely that interactions at a distance play an important role in GR action. To determine whether long range chromosomal associations play a role in transcription regulation by GR, we utilized a chromosome conformation capture-based technique (associated chromosome trap) to identify unknown, remote sequences that interact with the GR-induced Lipocalin2 (Lcn2) gene. Our screen revealed that the Lcn2 GRE interacts with the Ciz1 gene, nearly 30 kb upstream. Ciz1 was subsequently found to be a novel GR-responsive gene. The GRE proximal to the Lcn2 promoter apparently functions to regulate both the Lcn2 gene and the distal Ciz1 gene. Using quantitative chromosome conformation capture, we find that a loop structure is organized between these two genes. This structure is hormone-independent and present only in cell types where the genes are active. The strong correlation between gene expression and loop structure in different cell lines suggests that high order interactions play a role in determining tissue-specific gene regulation.

| S-EPMC2649095 | biostudies-literature

Advanced glycation end products regulate the receptor of AGEs epigenetically.

Project description:Advanced glycation end-products (AGEs) can boost their receptor of AGE (RAGE) expression through the downstream signaling pathway to facilitate AGE-RAGE interaction. In this regulation process, the primary signaling pathways are NF-κB and STAT3. However, the inhibition of these transcription factors cannot completely block the upregulation of RAGE, which indicates AGEs may also impact RAGE expression via other pathways. In this study, we revealed that AGEs can exhibit epigenetic impacts on RAGE expression. Here, we used carboxymethyl-lysine (CML) and carboxyethyl-lysine (CEL) to treat liver cells and discovered that AGEs can promote the demethylation of the RAGE promoter region. To verify this epigenetic modification, we employed dCAS9-DNMT3a with sgRNA to specifically modify the RAGE promoter region against the effect of carboxymethyl-lysine and carboxyethyl-lysine. The elevated RAGE expressions were partially repressed after AGE-induced hypomethylation statuses were reversed. Additionally, TET1 were also upregulated in AGE-treated cells, indicating AGEs may epigenetically modulate RAGE through the elevating TET1 level.

| S-EPMC9971228 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data