A5069903735- T-cell and B-cell Immunology
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
- MicroRNA in disease regulation
- CAR-T cell therapy research
- GDF15 and Related Biomarkers
- Genetic and Kidney Cyst Diseases
- RNA Interference and Gene Delivery
- interferon and immune responses
- Reproductive System and Pregnancy
- Ubiquitin and proteasome pathways
- NF-κB Signaling Pathways
- Genetic Syndromes and Imprinting
- Telomeres, Telomerase, and Senescence
- Signaling Pathways in Disease
- Neuroscience and Neuropharmacology Research
- Cancer-related gene regulation
- Neonatal Respiratory Health Research
Foundation for Research and Technology Hellas
2012-2023
University of Crete
2009-2023
Institute of Molecular Biology and Biotechnology
1998-2019
Yale University
2004-2010
FORTH Institute of Molecular Biology and Biotechnology
2009
Howard Hughes Medical Institute
2007-2008
Zero to Three
2005
The class II transactivator (CIITA) is a key regulatory factor that controls expression of the major histocompatibility complex (MHC) genes are essential components for antigen presentation and thus regulation immune response. We show here adenovirus E1A protein interferes with action CIITA inhibits both B-cell-specific gamma interferon (IFN-gamma)-induced MHC promoters. Transfection studies provide evidence functional role CREB-binding (CBP) in IFN-gamma CIITA-mediated promoter activation....
The class II transactivator (CIITA), the master regulator of tissue-specific and interferon gamma-inducible expression major histocompatibility complex genes, synergizes with histone acetylase coactivator CBP to activate gene transcription. Here we demonstrate that in addition CBP, PCAF binds CIITA both vivo vitro enhances CIITA-dependent transcriptional activation promoters. Accordingly, E1A mutants defective for or interaction show reduced ability suppressing activity. Interestingly,...
Endotoxin tolerance occurs to protect the organism from hyperactivation of innate immune responses, primarily mediated by macrophages. Regulation endotoxin at multiple levels cell responses and requires significant changes in gene expression. In process macrophage activation, induced expression microRNA (miR)-155 miR-146a contributes regulation inflammatory response tolerance. this article, we demonstrate that both miRNAs is coordinately regulated during a complex mechanism involves...
Abstract Mechanisms of tissue-specific gene expression regulation via 3D genome organization are poorly understood. Here we uncover the regulatory chromatin network developing T cells and identify SATB1, a organizer, enriched at anchors promoter-enhancer loops. We have generated T-cell specific Satb1 conditional knockout mouse which allows us to infer molecular mechanisms responsible for deregulation its immune system. H3K27ac HiChIP Hi-C experiments indicate that SATB1-dependent loops...
Cilia are present on nearly all cell types in mammals and perform remarkably diverse functions. However, the mechanisms underlying ciliogenesis unclear. Here, we cloned a previously uncharacterized highly conserved gene, stumpy, located mouse chromosome 7. Stumpy was ubiquitously expressed, conditional loss resulted complete penetrance of perinatal hydrocephalus (HC) severe polycystic kidney disease (PKD). We found that cilia stumpy mutant brain cells were absent or markedly deformed,...
The rates of activation and unitary properties Na + ‐activated K (K ) currents have been found to vary substantially in different types neurones. One class channels is encoded by the Slack gene. We now determined that alternative RNA splicing gives rise at least five transcripts for Slack, which produce differ their predicted cytoplasmic amino‐termini kinetic properties. Two these, termed Slack‐A channels, contain an amino‐terminus domain closely resembling another Slick Neuronal expression...
The T helper type 2 (Th2) cytokine genes Il4 , Il5 and Il13 are contained within a 140-kb region of mouse chromosome 11 their expression is controlled by locus control (LCR) embedded this locus. LCR composed number DNase I–hypersensitive sites (HSs), which believed to encompass the regulatory core LCR. To determine function these sites, mutant mice were generated in combinations HSs had been deleted from endogenous LCR, effect on Th2 was assessed through use vivo vitro models. These...
Significance Our study examines an important aspect of adaptive immunity, namely, the process effector T-cell activation, which leads to enhanced expression lineage-specific cytokine genes upon receptor (TCR) re-engagement. We found that TNF locus undergoes TCR-induced homologous allelic pairing, correlates with biallelic and requires a molecular motor, myosin VI. Furthermore, we identified role for VI in mediating transition RNA polymerase II (RNAPII) from pausing productive elongation at...
Abstract The infiltration and subsequent in situ subtype specification of monocytes to effector/inflammatory repair macrophages is indispensable for tissue upon acute sterile injury. However, the chromatin-level mediators regulatory events controlling this highly dynamic macrophage phenotype switch are not known. In study, we used a murine muscle injury model assess global chromatin accessibility gene expression dynamics infiltrating during physiological inflammation regeneration. We...
Significance In diploid organisms, trans-allelic interactions control gene expression, providing a tight spatial and temporal level of transcription regulation. Although homologous are quite abundant in various organisms such as Drosophila, plants, fungi, they have not been widely reported mammals. This article demonstrates that association is evident mammals involves the proximity Tnfα alleles prerequisite for biallelic expression gene. We believe phenomenon we describe here provides...
Class II transactivator (CIITA) is the master regulator of major histocompatibility complex class genes that regulates both B lymphocyte-specific and interferon γ-inducible expression. Here we identify protein regions examine mechanisms determine intracellular distribution CIITA. We show two separate CIITA mediate nuclear export: amino acids 1–114 408–550. Both interact with export receptor CRM-1. The region spanning 408–550 also determines its ability for homotypic self-association as well...
Intra-thymic T cell development is coordinated by the regulatory actions of SATB1 genome organizer. In this report, we show that involved in regulation transcription and splicing, both which displayed deregulation Satb1 knockout murine thymocytes. More importantly, characterized a novel protein isoform described its distinct biophysical behavior, implicating potential functional differences compared to commonly studied isoform. utilized prion-like domains transition through liquid-like...
Abstract Nuclear architecture and chromatin reorganization have recently been shown to orchestrate gene expression act as key players in developmental pathways. To investigate how regulatory elements the mouse CD8 locus are arranged space relation each other, three-dimensional fluorescence situ hybridization chromosome conformation capture techniques were employed monitor repositioning of its subchromosomal territory identify long-range interactions between different during development. Our...