While the biochemistry of gene transcription has been well studied, our understanding of how this process is organised in 3D within the intact nucleus is less well understood. Here we investigate the structure of actively transcribed chromatin and the architecture of its interaction with active RNA polymerase. For this analysis, we have used super-resolution microscopy to image the Drosophila melanogaster Y loops which represent huge, several megabases long, single transcription units. The Y loops provide a particularly amenable model system for transcriptionally active chromatin. We find that, although these transcribed loops are decondensed they are not organised as extended 10nm fibres, but rather they largely consist of chains of nucleosome clusters. The average width of each cluster is around 50nm. We find that foci of active RNA polymerase are generally located off the main fibre axis on the periphery of the nucleosome clusters. Foci of RNA polymerase and nascent transcripts are distributed around the Y loops rather than being clustered in individual transcription factories. However, as the RNA polymerase foci are considerably less prevalent than the nucleosome clusters, the organisation of this active chromatin into chains of nucleosome clusters is unlikely to be determined by the activity of the polymerases transcribing the Y loops. These results provide a foundation for understanding the topological relationship between chromatin and the process of gene transcription.
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http://dx.doi.org/10.1371/journal.pgen.1010654 | DOI Listing |
PLoS Pathog
January 2025
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Chikungunya virus (CHIKV) is an arthritogenic alphavirus that has re-emerged to cause large outbreaks of human infections worldwide. There are currently no approved antivirals for treatment of CHIKV infection. Recently, we reported that the ribonucleoside analog 4'-fluorouridine (4'-FlU) is a highly potent inhibitor of CHIKV replication, and targets the viral nsP4 RNA dependent RNA polymerase.
View Article and Find Full Text PDFPLoS One
January 2025
Arizona Humane Society, Phoenix, Arizona, United States of America.
SARS-CoV-2 is the cause of mild to severe acute respiratory disease that led to significant loss of human lives worldwide between 2019 and 2022. The virus has been detected in various animals including cats and dogs making it a major public health concern and a One Health issue. In this study, conjunctival and pharyngeal swabs (n = 350) and serum samples (n = 350) were collected between July and December 2020 from cats that were housed in an animal shelter and tested for the infection of SARS-CoV-2 using real time reverse-transcription polymerase chain reaction (rRT-PCR) that targeted the N1 and N2 genes, and a SARS-CoV-2 surrogate virus neutralization Test (sVNT), respectively.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Department of Spine, Orthopaedic Center, Guangdong Second Provincial General Hospital, Jinan University, Guangzhou, China.
Osteogenic differentiation of bone marrow stem cells (BMSCs) is essential for bone tissue regeneration and repair. However, this process is often hindered by an unstable differentiation influenced by local microenvironmental factors. While small extracellular vesicles (sEVs) derived from osteogenically induced adipose mesenchymal stem cells (ADSCs) reportedly can promote osteogenic differentiation of BMSCs, the underlying molecular mechanisms remain incompletely understood.
View Article and Find Full Text PDFCancer Res
January 2025
University of Maryland, Baltimore, Baltimore, Maryland, United States.
DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.
View Article and Find Full Text PDFDrug Des Devel Ther
January 2025
Department of Trauma Orthopedics, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272007, People's Republic of China.
Purpose: Osteosarcoma (OS) is the most common malignant tumor associated with poor patient outcomes and a limited availability of therapeutic agents. Scutellarein (SCU) is a monomeric flavone bioactive compound with potent anti-cancer activity. However, the effects and mechanisms of SCU on the growth of OS remain unknown.
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