Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CTCF binds to sites in the major histocompatibility complex that are rapidly reconfigured in response to interferon-gamma.

ABSTRACT: Activation of the major histocompatibility complex (MHC) by interferon-gamma (IFN-?) is a fundamental step in the adaptive immune response to pathogens. Here, we show that reorganization of chromatin loop domains in the MHC is evident within the first 30 min of IFN-? treatment of fibroblasts, and that further dynamic alterations occur up to 6 h. These very rapid changes occur at genomic sites which are occupied by CTCF and are close to IFN-?-inducible MHC genes. Early responses to IFN-? are thus initiated independently of CIITA, the master regulator of MHC class II genes and prepare the MHC for subsequent induction of transcription.

SUBMITTER: Ottaviani D

PROVIDER: S-EPMC3384298 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

CTCF binds to sites in the major histocompatibility complex that are rapidly reconfigured in response to interferon-gamma.

Ottaviani Diego D Lever Elliott E Mao Shihong S Christova Rossitza R Ogunkolade Babatunji W BW Jones Tania A TA Szary Jaroslaw J Aarum Johan J Mumin Muhammad A MA Pieri Christopher A CA Krawetz Stephen A SA Sheer Denise D

Nucleic acids research 20120225 12

Activation of the major histocompatibility complex (MHC) by interferon-gamma (IFN-γ) is a fundamental step in the adaptive immune response to pathogens. Here, we show that reorganization of chromatin loop domains in the MHC is evident within the first 30 min of IFN-γ treatment of fibroblasts, and that further dynamic alterations occur up to 6 h. These very rapid changes occur at genomic sites which are occupied by CTCF and are close to IFN-γ-inducible MHC genes. Early responses to IFN-γ are thus ...[more]

PMID: 22367884

Similar Datasets

An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.

Project description:Interferons (IFNs) induce transcription of major histocompatibility complex (MHC) class I genes through the conserved IFN consensus sequence (ICS) that contains an IFN response motif shared by many IFN-regulated genes. By screening mouse lambda ZAP expression libraries with the ICS as a probe, we isolated a cDNA clone encoding a protein that binds the ICS, designated ICSBP. Protein blot analysis with labeled oligonucleotide probes showed that ICSBP binds not only the MHC class I ICS but also IFN response motifs of many IFN-regulated genes, as well as a virus-inducible element of the IFN-beta gene. The ICSBP cDNA encodes 424 amino acids and a long 3' untranslated sequence. The N-terminal 115 amino acids correspond to a putative DNA-binding domain and show significant sequence similarity with other cloned IFN response factors (IRF-1 and IRF-2). Because of the structural similarity and shared binding specificity, we conclude that ICSBP is a third member of the IRF gene family, presumably playing a role in IFN- and virus-mediated regulation of many genes. Although IRF-1 and IRF-2 share some similarity in their C-terminal regions, ICSBP shows no similarity to IRF-1 or IRF-2 in this region, suggesting that it is more distantly related. We show that ICSBP mRNA is expressed predominantly in lymphoid tissues and is inducible preferentially by IFN-gamma. The induction by IFN-gamma appears to be predominant in lymphocytes and macrophages, implying that ICSBP plays a regulatory role in cells of the immune system. The presence of multiple factors that bind common IFN response motifs may partly account for the complexity and diversity of IFN action as well as IFN-regulated gene expression.

| S-EPMC53979 | biostudies-other

Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 3 inhibits gamma interferon and major histocompatibility complex class II expression.

Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) carries four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3), is expressed in latently infected primary effusion lymphoma (PEL) cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon (IFN) response. We now show that vIRF-3 also interferes with the type II interferon system and antigen presentation to the adaptive immune system. Starting with an analysis of the transcriptome, we show that vIRF-3 inhibits expression of major histocompatibility complex class II (MHC II) molecules: small interfering RNA (siRNA)-mediated knockdown of vIRF-3 in KSHV-infected PEL cell lines resulted in increased MHC II levels; overexpression of vIRF-3 in KSHV-negative B cells leads to downmodulation of MHC II. This regulation could be traced back to inhibition of class II transactivator (CIITA) transcription by vIRF-3. Reporter assays revealed that the gamma interferon (IFN-γ)-sensitive CIITA promoters PIV and PIII were inhibited by vIRF-3. Consistently, IFN-γ levels increased upon vIRF-3 knockdown in PEL cells. IFN-γ regulation by vIRF-3 was confirmed in reporter assays as well as by upregulation of typical IFN-γ target genes upon knockdown of vIRF-3 in PEL cells. In summary, we conclude that vIRF-3 contributes to the viral immunoevasion by downregulation of IFN-γ and CIITA and thus MHC II expression.

| S-EPMC3126280 | biostudies-literature

Cytomegalovirus infection and interferon-gamma modulate major histocompatibility complex class I expression on neural stem cells.

Project description:Cytomegalovirus (CMV) is the leading transmittable cause of congenital brain abnormalities in children and infection results in fatal ventriculoencephalitis in advanced acquired immunodeficiency syndrome (AIDS) patients. Pathology associated with CMV brain infection is seen predominantly in the periventricular region, an area known to harbor neural stem cells (NSCs). In the present study, using an adult model of murine CMV brain infection, the authors demonstrated that nestin-positive NSCs in the subventricular zone are susceptible to murine CMV infection. Furthermore, primary NSC cultures supported productive murine CMV replication with a 1000-fold increase in viral titers by 5 days post infection (d.p.i). Previous studies from the authors' laboratory demonstrated that CD8 lymphocytes were essential in protecting the brain against murine CMV infection. In the present study, the authors found that interferon (IFN)-gamma treatment increased the expression of major histocompatibility complex (MHC) class I on NSCs. Viral infection, on the other hand, inhibited this IFN-gamma-induced MHC up-regulation. In addition to increasing MHC class I expression, IFN-gamma (but not tumor necrosis factor [TNF]-alpha, interleukin [IL]-1 beta, or IL-10) also suppressed NSC proliferation in vitro. This decrease in proliferation was not accompanied by apoptosis or extracellular release of cellular lactate dehydrogenase (LDH), suggesting that the effects were not due to direct cytotoxicity. These studies demonstrate that NSCs are susceptible to murine CMV infection and inflammatory mediators, such as IFN-gamma, alter cellular characteristics which may have an impact on their reparative functions.

| S-EPMC2592495 | biostudies-literature

Interferon-gamma induces major histocompatibility class II transactivator (CIITA), which mediates collagen repression and major histocompatibility class II activation by human aortic smooth muscle cells.

Project description:Chronic inflammation in atherosclerosis is responsible for plaque instability through alterations in extracellular matrix. Previously, we demonstrated that major histocompatibility class II (MHC II) transactivator (CIITA) in a complex with regulatory factor for X box 5 (RFX5) is a crucial protein mediating interferon (IFN)-gamma-induced repression of collagen type I gene transcription in fibroblasts. This article demonstrates that, in smooth muscle cells (SMCs), IFN-gamma dramatically increases the expression of CIITA isoforms III and IV, with no increase in expression of CIITA isoform I. Expression of CIITA III and IV correlates with decreased collagen type I and increased MHC II gene expression. Exogenous expression of CIITA I, III, and IV, in transiently transfected SMCs, represses collagen type I promoters (COL1A1 and COL1A2) and activates MHC II promoter. Levels of CIITA and RFX5 increase in the nucleus of cells treated with IFN-gamma. Moreover, simvastatin lowers the IFN-gamma-induced expression of RFX5 and MHC II in addition to repressing collagen expression. However, simvastatin does not block the IFN-gamma-induced expression of CIITA III and IV, suggesting a CIITA-independent mechanism. This first demonstration that RFX5 and CIITA isoforms are expressed in SMCs after IFN-gamma stimulation suggest that CIITA could be a key factor in plaque stability in atherosclerosis.

| S-EPMC1388256 | biostudies-literature

major histocompatibility complex class II

Project description:amphibian MHC IIB1 Raw sequence reads

| PRJNA862637 | ENA

Interferon-gamma-activated macrophages infected with Burkholderia cenocepacia process and present bacterial antigens to T-cells by class I and II major histocompatibility complex molecules.

Project description:Burkholderia cenocepacia is an emerging opportunistic pathogen for people with cystic fibrosis and chronic granulomatous disease. Intracellular survival in macrophages within a membrane-bound vacuole (BcCV) that delays acidification and maturation into lysosomes is a hallmark of B. cenocepacia infection. Intracellular B. cenocepacia induce an inflammatory response leading to macrophage cell death by pyroptosis through the secretion of a bacterial deamidase that results in the activation of the pyrin inflammasome. However, how or whether infected macrophages can process and present B. cenocepacia antigens to activate T-cells has not been explored. Engulfed bacterial protein antigens are cleaved into small peptides in the late endosomal major histocompatibility class II complex (MHC) compartment (MIIC). Here, we demonstrate that BcCVs and MIICs have overlapping features and that interferon-gamma-activated macrophages infected with B. cenocepacia can process bacterial antigens for presentation by class II MHC molecules to CD4+ T-cells and by class I MHC molecules to CD8+ T-cells. Infected macrophages also release processed bacterial peptides into the extracellular medium, stabilizing empty class I MHC molecules of bystander cells. Together, we conclude that BcCVs acquire MIIC characteristics, supporting the notion that macrophages infected with B. cenocepacia contribute to establishing an adaptive immune response against the pathogen.

| S-EPMC7534305 | biostudies-literature

Major histocompatibility complex genomics and human disease.

Project description:Over several decades, various forms of genomic analysis of the human major histocompatibility complex (MHC) have been extremely successful in picking up many disease associations. This is to be expected, as the MHC region is one of the most gene-dense and polymorphic stretches of human DNA. It also encodes proteins critical to immunity, including several controlling antigen processing and presentation. Single-nucleotide polymorphism genotyping and human leukocyte antigen (HLA) imputation now permit the screening of large sample sets, a technique further facilitated by high-throughput sequencing. These methods promise to yield more precise contributions of MHC variants to disease. However, interpretation of MHC-disease associations in terms of the functions of variants has been problematic. Most studies confirm the paramount importance of class I and class II molecules, which are key to resistance to infection. Infection is likely driving the extreme variation of these genes across the human population, but this has been difficult to demonstrate. In contrast, many associations with autoimmune conditions have been shown to be specific to certain class I and class II alleles. Interestingly, conditions other than infections and autoimmunity are also associated with the MHC, including some cancers and neuropathies. These associations could be indirect, owing, for example, to the infectious history of a particular individual and selective pressures operating at the population level.

| S-EPMC4426292 | biostudies-literature

Structure and expression of major histocompatibility complex-binding protein 2, a 275-kDa zinc finger protein that binds to an enhancer of major histocompatibility complex class I genes.

Project description:We have isolated a cDNA encoding a transcription factor that binds to the enhancer of major histocompatibility complex (MHC) class I genes. MHC-binding protein 2 (MBP-2) is a 275-kDa protein, containing two sets of widely separated zinc fingers and a stretch of highly acidic amino acids, a putative transactivation domain. The two zinc finger regions, when expressed individually as bacterial fusion proteins, bind with highest affinity to the MHC class I gene enhancer. Several proteins found in mammalian nuclear extracts bind the MHC class I enhancer in an electrophoresis mobility shift assay. Only one of these, a ubiquitously expressed factor, forming a slow-migrating retarded complex, can be supershifted by a MBP-2 antiserum. The same antiserum also precipitates a protein of greater than 250 kDa from COS cells transfected with a MBP-2 expression vector. Our data indicate that MBP-2 is a transcription factor involved in the regulation of MHC class I gene expression.

| S-EPMC50046 | biostudies-other

The haplo-spliceo-transcriptome of the human Major Histocompatibility Complex

Project description:This SuperSeries is composed of the following subset Series: GSE22453: Custom MHC array analysis of lymphoblastoid cell lines GSE22454: Affymetrix Human Exon 1.0 ST array analysis of lymphoblastoid cell lines Refer to individual Series

2011-05-23 | E-GEOD-22455 | biostudies-arrayexpress

Major histocompatibility complex (MHC) class I gene expression in single neurons of the central nervous system: differential regulation by interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha.

Project description:This study examined the effect of the pro-inflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on the induction of MHC class I-related genes in functionally mature brain neurons derived from cultures of dissociated rat hippocampal tissue. Patch clamp electrophysiology combined with single cell RT-PCR demonstrated that approximately 50% of the untreated neurons contained mRNA for MHC class I heavy chains, while, with few exceptions, the cells failed to transcribe beta2-microglobulin and TAP1/TAP2 gene transcripts. No constitutive expression of MHC class I protein was detectable by confocal laser microscopy on the surface of neurons. All neurons transcribed the alpha-chain of the interferon-type II receptor (binding IFN-gamma) along with the p55 receptor for TNF-alpha. Sustained exposure to IFN-gamma resulted in transcription of beta2-microglobulin and TAP1/TAP2 genes and MHC class I surface expression in a minor part of the neurons, but did not alter their electrophysiological activities as assessed by whole cell electrophysiology. Suppression of neuronal electric activity by the sodium channel blocker tetrodotoxin drastically increased to almost 100% IFN-gamma-mediated induction of MHC class I chains, of both TAP transporters, and of membrane expression of MHC class I protein. The effect of tetrodotoxin is at least partly reverted by the neurotransmitter glutamate. In contrast to IFN-gamma, treatment with TNF-alpha did neither upregulate TAP1/TAP2 nor beta2-microglobulin gene expression, but induced MHC class I heavy chain gene transcription in all neurons. Consequently, no MHC class I molecules were detectable on the membranes of TNF-alpha-treated neurons.

| S-EPMC2196130 | 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