A5054635696- Pancreatic function and diabetes
- RNA modifications and cancer
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Liver physiology and pathology
- Chronic Lymphocytic Leukemia Research
- Drug Transport and Resistance Mechanisms
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- Cholesterol and Lipid Metabolism
- Cancer-related gene regulation
- DNA Repair Mechanisms
- FOXO transcription factor regulation
- Ubiquitin and proteasome pathways
- Lipid metabolism and biosynthesis
- Nuclear Receptors and Signaling
- RNA and protein synthesis mechanisms
- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
- Peroxisome Proliferator-Activated Receptors
- Cancer therapeutics and mechanisms
Foundation for Research and Technology Hellas
2001-2024
Institute of Molecular Biology and Biotechnology
2024
FORTH Institute of Molecular Biology and Biotechnology
1995-2021
Alexander Fleming Biomedical Sciences Research Center
2008-2020
Amsterdam UMC Location VUmc
2005
University of Crete
1993-1997
Boston University
1995
Transcription factors (TFs) direct gene expression by binding to DNA regulatory regions. To explore the evolution of regulation, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) determine experimentally genome-wide occupancy two TFs, CCAAT/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha, in livers five vertebrates. Although each TF displays highly conserved preferences, most is species-specific, aligned events present all species are rare....
We analyzed the ordered recruitment of factors to human alpha1 antitrypsin promoter around initial activation gene during enterocyte differentiation. found that a complete preinitiation complex, including phosphorylated RNA pol II, was assembled at long before transcriptional activation. The histone acetyltransferases CBP and P/CAF were recruited subsequently, but local hyperacetylation delayed. After transient Brahma homolog hBrm, remodeling neighboring nucleosome coincided with...
Cross-regulatory cascades between hepatic transcription factors have been implicated in the determination of phenotype. Analysis recruitments to regulatory regions and temporal spatial expression pattern main regulators during liver development revealed a gradual increase complexity autoregulatory cross-regulatory circuits. Within these circuits we identified core group six factors, which regulate each other downstream regulators. Changes promoter occupancy patterns included new...
Adaptation of liver to nutritional signals is regulated by several transcription factors that are modulated intracellular metabolites. Here, we demonstrate a factor network under the control hepatocyte nuclear 4α (HNF4α) coordinates reciprocal expression fatty acid transport and metabolizing enzymes during fasting feeding conditions. Hes6 identified as novel HNF4α target, which in normally fed animals, together with HNF4α, maintains PPARγ at low levels represses PPARα-regulated genes. During...
Gemcitabine (2′,2′-difluorodeoxycytidine) is a deoxycytidine analogue that activated by kinase (dCK) to its monophosphate and subsequently triphosphate dFdCTP, which incorporated into both RNA DNA, leading DNA damage. Multidrug resistance (MDR) characterised an overexpression of the membrane efflux pumps P-glycoprotein (P-gP) or multidrug resistance-associated protein (MRP). was tested against human melanoma, non-small-cell lung cancer, small-cell epidermoid carcinoma ovarian cancer cells...
Hepatocyte nuclear factor 4α (HNF-4α) (nuclear receptor 2A1) is an essential regulator of hepatocyte differentiation and function. Genetic molecular evidence suggests that the tissue-restricted expression HNF-4α regulated mainly at transcriptional level. As a step toward understanding mechanism involved in regulation human gene, we cloned analyzed 12.1-kb fragment its upstream region. Major DNase I-hypersensitive sites were found proximal promoter, first intron, more-upstream region...
The genetic code is an abstraction of how mRNA codons and tRNA anticodons molecularly interact during protein synthesis; the stability regulation this interaction remains largely unexplored. Here, we characterized expression genes quantitatively at multiple time points in two developing mouse tissues. We discovered that codon pools are highly stable over development simply reflect genomic background; contrast, precise gene families required to create corresponding transcriptomes. dynamic...
TGF-β signaling regulates a variety of cellular processes, including proliferation, apoptosis, differentiation, immune responses, and fibrogenesis. Here, we describe lysine methylation-mediated mechanism that controls the pro-fibrogenic activity TGF-β. We find methyltransferase Set9 potentiates by targeting Smad7, an inhibitory downstream effector. Smad7 methylation promotes interaction with E3 ligase Arkadia and, thus, ubiquitination-dependent degradation. Depletion or pharmacological...
Abstract Pioneering studies within the last few years have allowed in vitro expansion of tissue‐specific adult stem cells from a variety endoderm‐derived organs, including stomach, small intestine, and colon. Expansion these requires activation receptor Lgr5 by its ligand R‐spondin 1 is likely facilitated fact that healthy adults organs are highly proliferative. In many other such as liver, proliferating normally not abundant adulthood. However, upon injury, liver has strong regenerative...
Hepatocyte nuclear factors 1 and 4 (HNF-1 HNF-4) are liver-enriched transcription that function in the regulation of several liver-specific genes. HNF-1 activates genes containing promoters with binding sites. However, this factor negatively regulates its own expression other HNF-4-dependent lack sites their promoter region. This repression is exerted by a direct interaction AF2, main activation domain HNF-4. The dual functions gene suggest global regulator transcriptional network involved...
Hepatocyte nuclear factor-1 (HNF-1) plays an important role in the regulation of a large number genes expressed liver, kidney, and pancreatic β-cells. In exploring molecular mechanism involved HNF-1-dependent gene activation vivo chromatin context, we found that HNF-1 can physically interact with histone acetyltransferases (HATs) CREB-binding protein (CBP), p300/CBP-associated factor (P/CAF), Src-1, RAC3. The transcriptional potential on genome integrated promoter was strictly dependent...
Deoxycytidine kinase (dCK) catalyzes the rate-limiting step of deoxynucleoside salvage pathway in mammalian cells and plays a key role activation several pharmacologically important nucleoside analogs. Using highly specific polyclonal antibody raised against C-terminal peptide human dCK, we analyzed its subcellular localization by Western blots biochemically fractionated nuclear cytoplasmic fractions as well <i>in situ</i> immunochemistry. Native dCK was found to be located mainly cytoplasm...