It is well established that 5-methylcytosine (5mC) in genomic DNA of mammalian cells can be oxidized into 5-hydroxymethylcytosine (5hmC) and other derivates by DNA dioxygenase TETs. While conversion of 5mC to 5hmC plays an important role in active DNA demethylation through further oxidation steps, a certain proportion of 5hmCs remain in the genome. Although 5hmCs contribute to the flexibility of chromatin and protect bivalent promoters from hypermethylation, the direct effect of 5hmCs on gene transcription is unknown. In this present study, we have engineered a zinc-finger protein-based P16-specific DNA dioxygenase (P16-TET) to induce hydroxymethylation and demethylation in cancer cells. Our results demonstrate, for the first time, that although the hydroxymethylated alleles retain transcriptionally inactive, hydroxymethylation could increase the susceptibility of reactivation of methylated alleles.
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http://dx.doi.org/10.1080/15592294.2019.1700004 | DOI Listing |
Netw Neurosci
December 2024
Department of Cognition, Development and Education Psychology, University of Barcelona, Barcelona, Spain.
Memories are thought to use coding schemes that dynamically adjust their representational structure to maximize both persistence and efficiency. However, the nature of these coding scheme adjustments and their impact on the temporal evolution of memory after initial encoding is unclear. Here, we introduce the Segregation-to-Integration Transformation (SIT) model, a network formalization that offers a unified account of how the representational structure of a memory is transformed over time.
View Article and Find Full Text PDFMicrobes Infect
December 2024
Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany; Institute of Virology, Helmholtz Zentrum München, Munich, Germany. Electronic address:
Human endogenous retroviruses (HERVs), which are normally silenced by methylation or mutation, can be reactivated by a variety of environmental factors, including infection with exogenous viruses. In this work, we investigated the transcriptional activity of HERVs following infection of human liver cells (HepaRG) with human adenovirus C serotype 5 (HAdV-C5). HAdV-C5 infection results in reactivation of several HERV groups as well as differentially expressed genes.
View Article and Find Full Text PDFFront Oncol
December 2024
Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, United States.
Background: Richter's transformation (RT) in chronic lymphocytic leukemia (CLL) is associated with poor prognosis and requires prompt modifications in patient care. CLL patients are susceptible to severe infections due to immune dysregulation induced by their malignancy and immunosuppressive therapies.
Case Presentation: We present a case of a 63-year-old man with CLL who previously achieved remission and presented with a right inguinal mass.
Zhongguo Zhong Yao Za Zhi
October 2024
Guangdong Engineering Research Center for Disease Susceptibility and Traditional Chinese Medicine, Jinan University Guangzhou 510632, China Guangzhou Key Laboratory of Disease Susceptibility and Traditional Chinese Medicine Prevention and Treatment, Jinan University Guangzhou 510632, China Guangdong, Hong Kong and Macao Joint Laboratory of Universities, Guangdong Province, Jinan University Guangzhou 510632, China Institute of Traditional Chinese Medicine and Natural Medicines, Jinan University Guangzhou 510632, China.
Traditional Chinese medicine(TCM) theory suggests that "Shanghuo" is a comprehensive clinical symptom resulting from an imbalance of Yin and Yang. There is substantial clinical evidence showing that the consumption of warm or hot natured TCM can induce "Shanghuo". However, the pharmacological mechanisms and material basis of this phenomenon require further elucidation.
View Article and Find Full Text PDFCancer Res
December 2024
The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States.
Resistance of BRAF-mutant melanomas to targeted therapy arises from the ability of cells to enter a persister state, evade treatment with relative dormancy, and repopulate the tumor when reactivated. A better understanding of the temporal dynamics and specific pathways leading into and out of the persister state is needed to identify strategies to prevent treatment failure. Using spatial transcriptomics in patient-derived xenograft models, we captured clonal lineage evolution during treatment.
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