A5026469169- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Adrenal Hormones and Disorders
- RNA modifications and cancer
- Congenital heart defects research
- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- Gut microbiota and health
- Genomics and Chromatin Dynamics
- vaccines and immunoinformatics approaches
- Reproductive System and Pregnancy
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- High Altitude and Hypoxia
- Genomics and Phylogenetic Studies
- Cancer-related gene regulation
- Chromosomal and Genetic Variations
- Colorectal Cancer Screening and Detection
- Pluripotent Stem Cells Research
- Reproductive Biology and Fertility
- Nuclear Receptors and Signaling
- Mesenchymal stem cell research
University of Tartu
2008-2024
Estonian University of Life Sciences
2019
Competence Centre on Health Technologies (Estonia)
2019
University of Helsinki
2019
Helsinki University Hospital
2019
University of California, Los Angeles
2012-2018
Broad Center
2014-2016
Toniic Institute
2013
UCLA Health
2013
Film Independent
2011-2012
Background and Purpose— Recent evidence has implicated the genes for 5-lipoxygenase activating protein ( ALOX5AP ) phosphodiesterase 4D PDE4D as susceptibility stroke in Icelandic population. The aim of present study was to explore role these a central European population patients. Methods— A total 639 consecutive patients 736 unrelated population-based controls that had been matched age sex were examined using case-control design. Twenty-two single-nucleotide polymorphisms (SNPs) covering...
Despite correlations between histone methyltransferase (HMT) activity and gene regulation, direct evidence that HMT is responsible for activation sparse. We address the role of MLL1, a H3 lysine 4 (H3K4) critical maintaining hematopoietic stem cells (HSCs). Here, we show SET domain, thus dispensable HSCs supporting leukemogenesis driven by MLL-AF9 fusion oncoprotein. Upon Mll1 deletion, H4 16 (H4K16) acetylation selectively depleted at MLL1 target genes in conjunction with reduced...
Abstract Highlanders and lowlanders of Papua New Guinea have faced distinct environmental stress, such as hypoxia environment-specific pathogen exposure, respectively. In this study, we explored the top genomics regions candidate driver SNPs for selection in these two populations using newly sequenced whole-genomes 54 highlanders 74 lowlanders. We identified under - one highlanders, associated with red blood cell traits another lowlanders, which is white count – both potentially influencing...
Neutralizing autoantibodies to type I, but not II, interferons (IFNs) are found at high titers in almost every patient with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a disease caused by AIRE gene mutations that lead defects thymic T-cell selection. Combining genome-wide expression array real time RT-PCR assays, we here demonstrate antibodies against IFN-alpha cause highly significant down-regulation of interferon-stimulated cells from APECED patients' blood...
Plant homeodomain (PHD) fingers are often present in chromatin-binding proteins and have been shown to bind histone H3 N-terminal tails. Mutations the autoimmune regulator (AIRE) protein, which harbours two PHD fingers, cause a rare monogenic disease, polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE activates expression of tissue-specific antigens by directly binding through its first finger (AIRE-PHD1) tails non-methylated at K4 (H3K4me0). Here, we solution structure...
The Autoimmune Regulator (AIRE) protein is expressed in thymic medullary epithelial cells, where it promotes the ectopic expression of tissue-restricted antigens needed for efficient negative selection developing thymocytes. Mutations AIRE cause APECED syndrome, which characterized by a breakdown self-tolerance. molecular mechanism increases variety different genes remains unknown. Here, we studied AIRE-regulated using whole genome analysis and chromatin immunoprecipitation. We show that...
Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well chondrocytes 4 stages in vivo 2 during vitro differentiation. Network analysis delineated five tissue-specific modules; these modules chromatin state defined broad similarities cartilage specification maturation vivo, including progressive silencing...
Major vulnerability factors for psychiatric disorders such as depression, that often prevent complete remission and lead to relapses, are temperamental. In a rat model of clustered persistent high anxiety/low motivation, we have found overexpression glial-cell-line-derived neurotrophic factor (GDNF) by intra-striatally administered adeno-associated virus vector strikingly converts the passive coping style low exploratory rats into an active one, similar rats. This conversion behavioural...
The autoimmune regulator (AIRE) protein is a key mediator of the central tolerance for tissue specific antigens and involved in transcriptional control many thymic medullary epithelial cells (mTEC). Mutations AIRE gene cause rare disease named polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Here we report using GST pull-down assay, mass-spectrometry co-immunoprecipitation that heterotrimeric complex DNA-Dependent Protein Kinase (DNA-PK), consisting Ku70, Ku80 DNA-PK catalytic...
DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite progenitor survival. However, the transcription factors that promote DSB in B cells not known. Here we show MEF2C enhances expression and recombination progenitors, promoting repair, V(D)J cell Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor recovery after sub-lethal irradiation 5-fluorouracil injection....
Abstract Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and lastingly changes the gut microbiota community. However, physiological effects of – but not recent on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from deeply-phenotyped Estonian Microbiome Cohort (EstMB) we here utilised human-to-mouse faecal transplantation to explore long-term impacts use intestinal mucus function. While a healthy layer...
Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, physiological effects of - but not recent on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal transplantation to explore long-term impacts use intestinal mucus function. While a healthy layer protects...
Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in regulation inflammation far less understood, particularly for sex-related steroids. To determine contribution progesterone endothelium, we have characterized validated an vitro culture system which human umbilical vein endothelial cells constitutively express receptor (PR). Using next generation RNA-sequencing, identified a selective group cytokines that...
Abstract Background Monocyte-derived macrophages and dendritic cells (DCs) are important in inflammatory processes often used for immunotherapeutic approaches. Blood monocytes can be differentiated into DCs, which is accompanied with transcriptional changes many genes, including chemokines cell surface markers. Results To study the chromatin modifications associated this differentiation, we performed a genome wide analysis of histone H3 trimethylation on lysine 4 (H3K4me3) 27 (H3K27me3) as...
Abstract Colorectal cancer (CRC) is a challenging public health problem which successful treatment depends on the stage at diagnosis. Recently, CRC-specific microbiome signatures have been proposed as marker for CRC detection. Since many countries initiated screening programs, it would be useful to analyze in samples collected fecal immunochemical test (FIT) tubes occult blood testing. Therefore, we investigated impact of FIT and stabilization buffer microbial community structure evaluated...
Abstract STUDY QUESTION What is the effect of different oxygen (O 2 ) levels on transcriptomic profile bovine embryos during in vitro culture? SUMMARY ANSWER Embryos grown hypoxia (6% O from zygotes until blastocyst stage had highest formation rate, whereas normoxia (20% delayed reprogramming and embryonic genome activation, induced changes energy metabolism gene expression. WHAT IS KNOWN ALREADY Mammalian preimplantation embryo development a complex sequence events where, within week,...
Chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq) has revolutionized our understanding of chromatin-related biological processes. The method, however, requires thousands cells and therefore limited applications in situations where cell numbers are limited. Here we describe a novel method called Restriction Assisted Tagmentation Immunoprecipitation (RAT-ChIP) that enables global histone modification profiling from as few 100 cells. is simple, cost-effective...