Activation of Raf reduces the repressive histone mark H3K27me3 at the INK4a locus by inducing the H3K27me3 demethylase JMJD3. During hypoxia, the catalyitc activity of JMJD3 is reduced due to the limited availability of O as a substrate. In our study, we found that hypoxia prevented Raf-induced JMJD3 from demethylating H3K27me3 at the INK4a locus. Nonetheless, hypoxia did not prevent Raf signaling from inducing INK4a mRNA. Interestingly, we found that hypoxia strongly enhanced the active histone mark H3K4me3 at the INK4a locus by inhibiting the H3K4me3 demethylases JARID1A and JARID1B. Therefore, this study demonstrates that the O concentration in the microenvironment differentially affects the repressive methylation on K27 and the activating methylation on K4 at the INK4a locus by inhibiting the H3K27me3 and H3K4me3 demethylases.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/1873-3468.12375 | DOI Listing |
Cancer Med
January 2025
Faculty of Medical Sciences, Neuroscience Research Center, Lebanese University, Hadath, Lebanon.
Background: Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median survival of less than 15 months. Advancements in the field of epigenetics have expanded our understanding of cancer biology and helped explain the molecular heterogeneity of these tumors. B-cell-specific Moloney murine leukemia virus insertion site-1 (Bmi-1) is a member of the highly conserved polycomb group (PcG) protein family that acts as a transcriptional repressor of multiple genes, including those that determine cell proliferation and differentiation.
View Article and Find Full Text PDFFish Physiol Biochem
February 2025
Department of Marine Biosciences, Tokyo University of Marine Science and Technology, Konan 4-5-7, Minato, Tokyo, 108-8477, Japan.
Cell lines derived from fish tissues are resistant to premature senescence under typical culture conditions. Previously, we demonstrated that fish genomes do not have a p16/Arf locus and that the absence of this locus underlies the lack of senescence in cultured fish cells. However, other factors may also contribute to this resistance.
View Article and Find Full Text PDFInt J Mol Sci
September 2024
National Medical Research Center for Hematology, 125167 Moscow, Russia.
Tumor cells of acute lymphoblastic leukemia (ALL) may have various genetic abnormalities. Some of them lead to a complete loss of certain genes. Our aim was to reveal biallelic deletions of genes in Ph-negative T-ALL.
View Article and Find Full Text PDFGastro Hep Adv
May 2024
Translational Research Program, Benaroya Research Institute, Seattle, Washington.
Sci Rep
September 2024
Fels Cancer Institute for Personalized Medicine, Temple University Lewis Katz School of Medicine, AHP Bldg., Room 308, 3307 North Broad St., Philadelphia, PA, 19140, USA.
Prostate cancer (PCa) is the most common cancer diagnosed in men worldwide and was the second leading cause of cancer-related deaths in US males in 2022. Prostate cancer also represents the second highest cancer mortality disparity between non-Hispanic blacks and whites. However, there is a relatively small number of prostate normal and cancer cell lines compared to other cancers.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!