Genetics of gene regulation in disease

Information People Publications

Leaders

Sami Heikkinen

Research Director

School of Medicine, Biomedicine

We focus on the identification and molecular characterization of human genetic variation that alters the gene regulatory capacity of transcription factors and contributes to diseases with identified genetic component like type 2 diabetes or Alzheimer’s disease. Our research on the metabolic front utilizes a combination of mouse genetics and detailed genome-wide mapping of e.g. gene expression and chromatin activities at tissue and single-cell levels, with an aim to extrapolate the main findings to human metabolic genetics through conserved metabolic regulatory cascades. For neurodegenerative diseases we collaborate widely with the research teams of the UEF Neuro RC.

The identification and mechanistic characterization of new, truly causal human genetic variants in complex diseases offer tools for improved disease prediction, subtyping and personalized medicine solutions.

Funding

Academy of Finland, Finnish Diabetes Research Foundation, University of Eastern Finland

Cooperation

Luke Norton, PhD

University of Texas Health San Antonio
Timo Lakka, PhD, MD

University of Eastern Finland, Institute of Biomedicine
Arto Mannermaa, PhD

University of Eastern Finland, Clinical Pathology and Forensic Medicine

Keywords

chromatin chromatin interactions epigenetics gene expression gene regulation genetic variants genetics genomics regulatory interactions transcription regulation

Leaders

Sami Heikkinen

Research Director

School of Medicine, Biomedicine

Doctoral Researchers

Juho Mononen

Doctoral Researcher

School of Medicine, Biomedicine

Publications

65 items

Genetics of gene regulation in disease

Leaders

Sami Heikkinen

Cooperation

Keywords

Leaders

Sami Heikkinen

Doctoral Researchers

Juho Mononen

Integrative analysis of liver-specific non-coding regulatory SNPs associated with the risk of coronary artery disease

Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure

The debatable presence of PIWI-interacting RNAs in invasive breast cancer

Toxicological transcriptome of human airway constructs after exposure to indoor air particulate matter: In search of relevant pathways of moisture damage-associated health effects

Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

MicroRNAs Associated With Biological Pathways of Left- And Right-sided Colorectal Cancer

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Abdominal adiposity and cardiometabolic risk factors in children and adolescents: a Mendelian randomization analysis

HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells

Multi-Ancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

The Diabetes Gene and Wnt Pathway Effector TCF7L2 Regulates Adipocyte Development and Function

Integration of VDR genome wide binding and GWAS genetic variation data reveals co-occurrence of VDR and NF-kappaB binding that is linked to immune phenotypes

NRF2 regulates endothelial glycolysis and proliferation with miR-93 and mediates the effects of oxidized phospholipids on endothelial activation

The Effects of Sequence Variation on Genome-wide NRF2 Binding - New Target Genes and Regulatory SNPs

Gene Expression Mapping of Histone Deacetylases and Co-factors, and Correlation with Survival Time and 1H-HRMAS Metabolomic Profile in Human Gliomas

Patterns of Genome-Wide VDR Locations

SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner

The mechanisms of genome-wide target gene regulation by TCF7L2 in liver cells

The transcriptional regulator BCL6 participates in the secondary gene regulatory response to vitamin D

Dynamics of 1&#945 ,25-dihydroxyvitamin D3-dependent chromatin accessibility of early vitamin D receptor target genes

Chromatin acetylation at transcription start sites and vitamin D receptor binding regions relates to effects of 1alfa,25-dihydroxyvitamin D3 and histone deacetylase inhibitors on gene expression

Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages

Proto-oncogene PIM-1 is a novel estrogen receptor target associating with high grade breast tumors

The First Genome-wide View of Vitamin D Receptor Locations and Their Mechanistic Implications

The activation of hepatic and muscle polyamine catabolism improves glucose homeostasis

The gene for the transcription factor BHLHE40/DEC1/stra13 is a dynamically regulated primary target of the vitamin D receptor

Nuclear hormone 1&#945 ,25-dihydroxyvitamin D3 elicits a genome-wide shift in the locations of VDR chromatin occupancy

Activated polyamine catabolism leads to low cholesterol levels by enhancing bile acid synthesis

Partial hexokinase II knocout results in acute ischemia-reperfusion damage in skeletal muscle of male, but not female, mice

The Down-regulation of the Human MYC Gene by the Nuclear Hormone 1&#945 ,25-dihydroxyvitamin D3 is Associated with Cycling of Corepressors and Histone Deacetylases

Enhanced polyamine catabolism alters homeostatic control of white adipose tissue mass, energy expenditure, and glucose metabolism

PPARgamma in human and mouse physiology

Phosphorylation barriers to skeletal and cardiac muscle glucose uptakes in high-fat-fed mice. Studies in mice with a 50 % reduction of hexokinase II

Systematic gene expression mapping clusters nuclear receptors according to their function in the brain

Mice with targeted disruption of spermidine/spermine N1-acetyltransferese gene maintain nearly normal tissue polyamine homeostasis but show signs of insulin resistance upon aging

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N1 -acetyltransferase

Transcriptional targeting of virus-mediated gene transfer by the human hexokinase II promoter

Type I interferon response against viral and non-viral gene transfer in human tumor and primary cell lines

Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse

Analysis of the human hexokinase II promoter in vivo: lack of insulin response within 4.0 kb

Glucose Metabolism in Heterozygous Hexokinase II Knock-out Mice

Hexokinase II partial knockout impairs exercise-stimulated glucose uptake in oxidative muscles of mice

Mutations in the cardiac myosin-binding protein C gene are the predominant cause of familial hypertrophic cardiomyopathy in eastern Finland

Concurrent overexpression of ornithine decarboxylase and spermidine/spermine N1-acetyltransferase further accelerates the catabolism of hepatic polyamines in transgenic mice

Mouse hexokinase II gene: structure, cDNA, promoter analysis, and expression pattern

Hexokinase II-deficient mice: prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes

The codon 64 polymorphism of the beta3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients

Different regulation of free fatty acid levels and glucose oxidation by the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and the promoter variant (A-3826G) of the uncoupling protein 1 gene in familial combined hyperlipidemia

Glucokinase gene islet promoter region variant (G->A) at nucleotide -30 is not associated with reduced insulin secretion in Finns

Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on basal metabolic rate in obese Finns

Variants of the fatty acid-binding protein 2 gene are not associated with coronary heart disease in nondiabetic subjects and in patients with NIDDM

Codon 54 polymorphism of the human intestinal fatty acid binding protein 2 gene is associated with dyslipidemias but not with insulin resistance in patients with familial combined hyperlipidemia

New variants in the glycogen synthase gene (GIn71His, Met416Val) in patients with NIDDM from eastern Finland

Polymorphism of the Beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns

The ala54thr polymorphism of the fatty acid binding protein 2 gene does not influence insulin sensitivity in Finnish nondiabetic and NIDDM subjects

The trp64arg polymorphism of the beta3-adrenergic receptor gene

Threonine allele in codon 54 of the fatty acid binding protein 2 gene does not modify the fatty acid composition of serum lipids in obese subjects

Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects