Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
The functional role of enhancer-promoter configurations in transcription regulation remains poorly understood, despite the wide range of linear genomic distance and relative enhancer positioning observed in endogenous contexts. While canonical models suggest that enhancers operate independently of genomic position, technical limitations have obscured insights on transcriptional kinetics. Here, we employ single-cell MS2/MCP-based live imaging in embryos to systematically analyze transcriptional dynamics driven by sub-10kb enhancer-promoter arrangements. Kinetic analyses reveal that while linear enhancer-promoter distance moderately tunes transcriptional output, downstream enhancer positioning reduces mRNA output by 70%. Each configuration modulates distinct transcriptional parameters: linear distance governs initiation kinetics, while relative enhancer positioning dictates transcriptional stability. These effects are consistent across varied enhancer and reporter sequences, revealing configuration-dependent -regulatory element arrangement as an intrinsic mechanism for transcriptional fine-tuning. This work challenges the paradigm of configuration-independent enhancer function and establishes a framework to dissect the interplay between genome architecture and -acting factors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363964 | PMC |
| http://dx.doi.org/10.1101/2025.08.14.670187 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dual function of itaconic acid from against .
Plant Dis
September 2025
Shenyang Agricultural University, College of Plant Protection, Nematology Institute of Northern China, Shenyang, China;
Root-knot nematodes (Meloidogyne spp.) cause catastrophic yield losses in global agriculture. This study identified itaconic acid (IA), through comparative metabolomic analysis (the study of small molecules in biological systems), as a key virulence-related metabolite produced by the fungus Trichoderma citrinoviride Snef1910.
View Article and Find Full Text PDFConnecting the Dots: Hepatic Steatosis as a Central Player in the Choreography of the Liver-Cardiovascular-Kidney-Metabolic Syndrome.
Heart Lung Circ
September 2025
Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia; Medical School, The University of Western Australia, Perth, WA, Australia; Curtin Medical School, Curtin University, Bentley, WA, Australia. Electronic address:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, with a reach extending beyond the liver to include other metabolic syndrome-related disorders. Cardiovascular disease and type 2 diabetes mellitus are recognised non-communicable disorders and often downstream complications of MASLD and share similar risk factors. However, MASLD has not been afforded parity alongside other cardiometabolic non-communicable disorders, including the cardiovascular-kidney-metabolic (CKM) syndrome.
View Article and Find Full Text PDFReprogramming the immunologically cold landscape of prostate cancer through MAOA inhibition.
J Immunother Cancer
September 2025
Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA
Prostate cancer (PC) is notoriously known for exhibiting an immunologically cold phenotype in the tumor immune microenvironment (TIME), leading to the need for interventions to enhance immunotherapy efficacy. Recent findings by Zhao in the identified stromal monoamine oxidase A (MAOA), a key enzyme that degrades monoamine neurotransmitters and plays a role in the neuroendocrine system, as a critical regulator of the immune response to PC. Altering MAOA levels in myofibroblastic cancer-associated fibroblasts, either genetically or pharmacologically, can reprogram PC's TIME to modulate CD8 T cell-mediated cytotoxicity through the WNT5A-Ca²-NFATC1 signaling axis, highlighting the stromal influences on CD8 T cell cytotoxic activity within the TIME.
View Article and Find Full Text PDFA large left ventricular sub-mitral thrombus in the absence of sub-mitral aneurysm in a patient with colorectal adenocarcinoma.
BMJ Case Rep
September 2025
Cardiology, JIPMER, Puducherry, India.
A left ventricular sub-mitral thrombus without an aneurysm is a previously unreported rare occurrence. We aim to bring attention to this finding in a case of colorectal adenocarcinoma.An early 60s-year-old female presented with bleeding per rectum, weight loss and fatigue and was found to have colorectal carcinoma with metastasis based on examination, imaging and biopsy findings.
View Article and Find Full Text PDFLeading through expertise: a qualitative study of clinicians' experience of a paediatric clinical trial for displaced medial epicondyle fracture.
Bone Jt Open
September 2025
Kadoorie, Oxford Trauma and Emergency Care, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, UK.
Aims: We sought to explore staff experience of a paediatric randomized controlled trial (RCT), comparing operative fixation and nonoperative treatment for displaced medial epicondyle fractures.
Methods: A total of 20 staff (eight surgeons and 12 research delivery staff) recruiting to the RCT in 18 NHS Trusts across the UK took part in a telephone/online qualitative interview. Interviews were informed by Heideggerian Phenomenology and thematic analysis.