Information about the time and place of gene transcription, which until recently was only possible by extensive experimental analysis, can now be predicted through in silico analysis. Using the human RANTES/CCL5 promoter, we show that organizational features of promoters derived from promoter sequences contain information about the spatial and temporal 'functional context' of expression.
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http://dx.doi.org/10.1016/s0168-9525(02)02591-x | DOI Listing |
Nat Commun
January 2025
Gene Regulation Laboratory, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS, Oxford, UK.
Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
MatTek Corporation, Ashland, MA 01721, USA.
Risk of lung damage from inhaled chemicals or substances has long been assessed using animal models. However, New Approach Methodologies (NAMs) that replace, reduce, and/or refine the use of animals in safety testing such as 2D and 3D cultures are increasingly being used to understand human-relevant toxicity responses and for the assessment of hazard identification. Here we review 2D and 3D lung models in terms of their application for inhalation toxicity assessment.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, 2450 Copenhagen, Denmark.
microRNA-22 (miR-22) plays a pivotal role in the regulation of metabolic processes and has emerged as a therapeutic target in metabolic disorders, including obesity, type 2 diabetes, and metabolic-associated liver diseases. While miR-22 exhibits context-dependent effects, promoting or inhibiting metabolic pathways depending on tissue and condition, current research highlights its therapeutic potential, particularly through inhibition strategies using chemically modified antisense oligonucleotides. This review examines the dual regulatory functions of miR-22 across key metabolic pathways, offering perspectives on its integration into next-generation diagnostic and therapeutic approaches while acknowledging the complexities of its roles in metabolic homeostasis.
View Article and Find Full Text PDFMedicina (Kaunas)
January 2025
Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, "Victor Babeş" University of Medicine and Pharmacy Timișoara, Eftimie Murgu Square No. 2, 300041 Timișoara, Romania.
: Sodium butyrate (NaB) is a potent modulator of cancer-related gene networks. However, its precise mechanisms of action and effects at elevated doses remain insufficiently explored. This study investigated the impact of NaB at physiologically relevant doses on key cellular metrics (viability, confluence, cell number, morphology, nuclear integrity) and a comprehensive set of apoptosis and proliferation regulators (including underexplored genes) in colorectal cancer (CRC) cells.
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