The transcriptional machinery is thought to dissociate from DNA during replication. Certain proteins, termed epigenetic marks, must be transferred from parent to daughter DNA strands in order to maintain the memory of transcriptional states. These proteins are believed to re-initiate rebuilding of chromatin structure, which ultimately recruits RNA polymerase II (Pol II) to the newly replicated daughter strands. It is believed that Pol II is recruited back to active genes only after chromatin is rebuilt. However, there is little experimental evidence addressing the central questions of when and how Pol II is recruited back to the daughter strands and resumes transcription. Here we show that immediately after passage of the replication fork, Pol II in complex with other general transcription proteins and immature RNA re-associates with active genes on both leading and lagging strands of nascent DNA, and rapidly resumes transcription. This suggests that the transcriptionally active Pol II complex is retained in close proximity to DNA, with a Pol II-PCNA interaction potentially underlying this retention. These findings indicate that the Pol II machinery may not require epigenetic marks to be recruited to the newly synthesized DNA during the transition from DNA replication to resumption of transcription.
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http://dx.doi.org/10.1038/s41586-023-06341-9 | DOI Listing |
Mol Pharm
January 2025
State Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China.
Natural killer (NK) cell immunotherapy is a significant category in tumor therapy due to its potent tumor-killing and immunomodulatory effects. This research delves into exploring the mechanisms underlying the ability of amoxicillin to boost NK cell cytotoxicity in NK cell immunotherapy. Amoxicillin significantly enhances the cytotoxic activity of NK-92MI cells against MCF-7 cells by triggering the initiation of a cytolytic program in target cell-deficient NK-92MI cells and augmenting the degranulation level of NK-92MI cells in the presence of target cells.
View Article and Find Full Text PDFObjective: Aim: The aim of the study is to consists in the theoretical analysis of the results of modern genetic studies of human cognitive abilities as a key to successful education and upbringing.
Patients And Methods: Materials and Methods: To solve the tasks and achieve the goal of the article, we used general scientific methods of the theoretical level (analysis, synthesis, comparison, systematization, generalization of scientific and theoretical data), regarding the influence of heredity and environment on human cognitive ability.
Conclusion: Conclusions: Human cognitive abilities develop under the influence of both genetic and environmental factors.
Proc Natl Acad Sci U S A
February 2025
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Classical tissue recombination experiments demonstrate that cell-fate determination along the anterior-posterior axis of the Müllerian duct occurs prior to postnatal day 7 in mice. However, little is known about how these cell types are maintained in adults. In this study, we provide genetic evidence that a balance between antagonistic retinoic acid (RA) and estrogen signaling activity is required to maintain simple columnar cell fate in adult uterine epithelium.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Center for Medical Research and Innovation, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, Chinese Academy of Medical Sciences (RU069), Medical College of Fudan University, Shanghai 201399, China.
Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine.
View Article and Find Full Text PDFBiochemistry
January 2025
Transcription Regulation Lab, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Third Milestone, Faridabad-Gurgaon Expressway, Faridabad 121001, India.
Bacterial flagella are complex molecular motors that are essential for locomotion and host colonization. They consist of 30 different proteins expressed in varying stoichiometries. Their assembly and function are governed by a hierarchical transcriptional regulatory network with multiple checkpoints primarily regulated by sigma factors.
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