A5026469169- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Adrenal Hormones and Disorders
- RNA modifications and cancer
- Congenital heart defects research
- Zebrafish Biomedical Research Applications
- CRISPR and Genetic Engineering
- Reproductive Biology and Fertility
- Immunotherapy and Immune Responses
- Mesenchymal stem cell research
- Acute Myeloid Leukemia Research
- Gut microbiota and health
- Genomics and Chromatin Dynamics
- Immune cells in cancer
- Birth, Development, and Health
- Colorectal Cancer Screening and Detection
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- vaccines and immunoinformatics approaches
- Cytokine Signaling Pathways and Interactions
- Cancer-related gene regulation
- Pluripotent Stem Cells Research
- Nuclear Receptors and Signaling
- Genomics and Phylogenetic Studies
University of Tartu
2009-2025
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...
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...
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...
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...
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...
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....
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 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...
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...
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...
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...
Abstract Modification of mRNA by methylation is involved in post-transcriptional regulation gene expression affecting the splicing, transport, stability and translation mRNA. Methylation adenosine at N 6 (m A) one most common important cellular modification occurring eukaryotes. Evidence that m A stress response its dysregulation may contribute to pathogenesis neuropsychiatric disorders accumulating. We have examined acute subchronic (up 18 days once per day intraperitoneally) effect first...