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/10.1002/1873-3468.12375DOI Listing

Publication Analysis

Top Keywords

ink4a locus
20
h3k27me3 h3k4me3
8
h3k4me3 ink4a
8
histone mark
8
h3k27me3 ink4a
8
locus inhibiting
8
h3k4me3 demethylases
8
ink4a
6
h3k27me3
5
locus
5

Similar Publications

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 PDF

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 PDF

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 PDF
Article Synopsis
  • The study investigates how the chromatin and protein expressions of colonic epithelial cells differ between healthy individuals and patients with ulcerative colitis (UC), highlighting the role of epithelial dysfunction in UC pathology.
  • Researchers sorted and analyzed epithelial cells from colon biopsies of healthy controls and UC patients to uncover these differences in proteome and chromatin accessibility.
  • Results show significant protein elevation linked to inflammation in UC, with a notable reduction of the water channel aquaporin 8, indicating specific epigenetic mechanisms that influence protein expression in health vs. disease.
View Article and Find Full Text PDF

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 PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!