We present a biophysical model of promoter search by Escherichia coli RNA polymerase. We use an unconventional weight matrix derived from promoter strength data to extract the energy landscape common to a large set of known promoters. This exhibits a continuous strengthening of the binding energy when approaching the transcription start site from either side. During promoter search, the RNA polymerase slides along the DNA double helix (one-dimensional diffusion) after randomly binding to it. We discuss the possibility that the sliding has a sequence-dependent component, which implies that the energy landscape influences the movement with respect to speed, direction and efficiency. Based on this assumption, we relate the obtained energy landscape around the promoters to the one-dimensional diffusion of the RNA polymerase. Our analytical results suggest that the sequence-dependent random walk slows down and gets directed upon entering a region of 500 bp around the transcription start site, which significantly increases the efficiency of promoter search. These results may explain how the RNA polymerase is able to find the promoter in biologically relevant times out of a vast excess of non-target sites. Moreover, they provide evidence for a sequence-dependent component of one-dimensional diffusion.
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http://dx.doi.org/10.1016/j.jtbi.2009.05.006 | DOI Listing |
Nat Chem Biol
January 2025
Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.
View Article and Find Full Text PDFMedicine (Baltimore)
November 2024
Yantai Yuhuangding Hospital, Shandong, China.
Background: The neutrophil-mediated generation of neutrophil extracellular traps (NETs) results in an augmented inflammatory response and cellular tissue injury during acute myocardial infarction (AMI). Through the analysis of public database information, we discovered and confirmed putative critical genes involved in NETs-mediated AMI.
Methods: The AMI dataset GSE66360 and the single-cell dataset GSE163465 were downloaded from the Gene Expression Omnibus database.
Alzheimers Dement
January 2025
Center for Geriatric Medicine, Key Laboratory of Alzheimer's Disease of Zhejiang Province, The First Affiliated Hospital and Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Introduction: Interferon-induced transmembrane protein 3 (IFITM3) modulates γ-secretase in Alzheimer's Disease (AD). Although IFITM3 knockout reduces amyloid β protein (Aβ) production, its cell-specific effect on AD remains unclear.
Methods: Single nucleus RNA sequencing (snRNA-seq) was used to assess IFITM3 expression.
New Phytol
January 2025
Section for Plant Biochemistry and Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, 1871, Frederiksberg, Denmark.
Lupins are promising protein crops that accumulate toxic quinolizidine alkaloids (QAs) in the seeds, complicating their end-use. QAs are synthesized in green organs (leaves, stems, and pods) and a subset of them is transported to the seeds during fruit development. The exact sites of biosynthesis and accumulation remain unknown; however, mesophyll cells have been proposed as sources, and epidermal cells as sinks.
View Article and Find Full Text PDFBiomater Res
January 2025
Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.
Cutaneous photoaging, induced by chronic exposure to ultraviolet (UV) radiation, typically manifests as alterations in both the physical appearance and functional properties of the skin and may predispose individuals to cancer development. Recent studies have demonstrated the reparative potential of exosomes derived from mesenchymal stem cells in addressing skin damage, while specific reports highlight their efficacy in ameliorating skin photoaging. However, the precise role of exosomes derived from human hair follicle mesenchymal stem cells (HFMSC-Exos) in the context of cutaneous photoaging remains largely unexplored.
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