Class 1 integrons are widespread genetic elements responsible for dissemination of antibiotic resistance among Gram-negative bacteria. Integrons allow bacteria to capture and express gene cassettes (GCs) via an integrase (IntI1) and a promoter (Pc) contained in the integron functional platform. GCs are transcribed from Pc, of which 13 variants of different strengths have been described, or, occasionally, from both Pc and a second promoter (P2). The intI1 promoter (PintI1) is repressed by LexA, which is the transcriptional repressor of the global regulatory SOS response network. Moreover, PintI1 lies face to face with Pc and overlaps P2, both configurations being propitious to transcriptional interference (TI). In this study, we analyzed possible transcriptional interference by quantifying transcripts produced from Pc, P2, and PintI1. We found that the Pc promoter interferes with the level of intI1 transcription but that this effect depends on the Pc variant: the strong Pc variant prevents intI1 expression, in contrast to the other variants. Although P2 formation results in LexA binding site disruption and thus prevents SOS regulation of intI1 expression, P2 does not interfere with PintI1. These findings reveal a tight relationship between GC and integrase expression.
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http://dx.doi.org/10.1128/JB.05246-11 | DOI Listing |
Int J Mol Sci
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Department of Neuroregeneration, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
Semaphorin 3A (Sema3A) is an axon guidance molecule, which is also abundant in the adult central nervous system (CNS), particularly in perineuronal nets (PNNs). PNNs are extracellular matrix structures that restrict plasticity. The cellular sources of Sema3A in PNNs are unknown.
View Article and Find Full Text PDFSci Rep
January 2025
Sorbonne Université, CNRS, Inserm, Centre d'Immunologie et des Maladies Infectieuses, CIMI, F-75013 Paris, France.
Malaria is caused by protozoan parasites of the genus Plasmodium and remains a global health concern. The parasite has a highly adaptable life cycle comprising successive rounds of asexual replication in a vertebrate host and sexual maturation in the mosquito vector Anopheles. Genetic manipulation of the parasite has been instrumental for deciphering the function of Plasmodium genes.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Institute for Biomedicine and Glycomics, School of Environment and Science, Griffith University, 46 Don Young Road, Brisbane QLD 4111, Australia., Brisbane, QLD 4111, Australia.
While many genetic tools exist for zebrafish, this animal model still lacks robust gene-silencing and microRNA-delivery technologies enabling spatio-temporal control and traceability. We have recently demonstrated that engineered pri-miR backbones can trigger stable gene knockdown and/or express microRNA(s) of choice in this organism. However, this miRNA-expressing technology presents important limitations.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Bacterial artificial chromosome transgenic models, including most Cre-recombinases, enable potent interrogation of gene function in vivo but require rigorous validation as limitations emerge. Due to its high relevance to metabolic studies, we perform comprehensive analysis of the Ucp1-Cre line which is widely used for brown fat research. Hemizygotes exhibit major brown and white fat transcriptomic dysregulation, indicating potential altered tissue function.
View Article and Find Full Text PDFCancer Sci
January 2025
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Effective therapeutic strategies for epithelioid sarcoma (EpS), a high-grade soft tissue sarcoma characterized by loss of integrase interactor 1 (INI1), have not yet been developed. The present study therefore investigated the association between INI1 loss and upregulation of the aurora kinase A (AURKA)/polo-like kinase 1 (PLK1)/cell division cycle 25C (CDC25C) axis, as well as the therapeutic relevance of this axis in EpS. Notably, our findings showed that the reintroduction of INI1 in VA-ES-BJ cells significantly reduced proliferation, mitigated tumorigenicity, and negatively regulated the expression of AURKA and its downstream effectors, as well as the activation of PLK1 and CDC25C.
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