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Exploring oncogenic roles and clinical significance of EZH2: focus on non-canonical activities.
Ther Adv Med Oncol
January 2025
Department of Molecular Biology of Cancer, Medical University of Lodz, Mazowiecka 6/8, Lodz 92-215, Poland.
The enhancer of zeste homolog 2 (EZH2) is a catalytic component of Polycomb repressive complex 2 (PRC2) mediating the methylation of histone 3 lysine 27 (H3K27me3) and hence the epigenetic repression of target genes, known as canonical function. Growing evidence indicates that EZH2 has non-canonical roles that are exerted as PRC2-dependent and PRC2-independent methylation of non-histone proteins, and methyltransferase-independent interactions of EZH2 with various proteins contributing to gene expression regulation and alterations in the protein stability. is frequently mutated and/or its expression is deregulated in various cancer types.
View Article and Find Full Text PDFGestational diabetes mellitus causes genome hyper-methylation of oocyte via increased EZH2.
Nat Commun
January 2025
College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, 266109, People's Republic of China.
Gestational diabetes mellitus (GDM), a common pregnancy disease, has long-term negative effects on offspring health. Epigenetic changes may have important contributions to that, but the underlying mechanisms are not well understood. Here, we report the influence of GDM on DNA methylation of offspring (GDF1) oocytes and the possible mechanisms.
View Article and Find Full Text PDFAbnormal H3K27me3 underlies degenerative spermatogonial stem cells in cryptorchid testis.
Development
January 2025
Department of Histology and Cell Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
Article Synopsis
- Cryptorchidism is a common congenital condition in newborn males where one or both testes fail to descend into the scrotum, leading to potential infertility due to azoospermia.
- Research using a mouse model of surgically induced cryptorchidism revealed changes in the epigenetic markers H3K27me3 and H3K9me3 in spermatogonial cells, with a specific loss of H3K27me3 linked to gene activation related to development and apoptosis.
- The study indicates that elevated temperatures may enhance the activity of enzymes that demethylate H3K27, contributing to mRNA dysregulation and potentially impacting spermatogonial function.
SP140 represses specific loci by recruiting polycomb repressive complex 2 and NuRD complex.
Nucleic Acids Res
December 2024
IFOM ETS, The AIRC Institute of Molecular Oncology, Via Adamello 16, 16039 Milano, Italy.
SP140, a lymphocytic-restricted protein, is an epigenetic reader working as a corepressor of genes implicated in inflammation and orchestrating macrophage transcriptional programs to maintain cellular identity. Reduced SP140 expression is associated both to autoimmune diseases and blood cancers. However, the molecular mechanisms that link SP140 altered protein levels to detrimental effects on the immune response and cellular growth, as well as the interactors through which SP140 promotes gene silencing, remain elusive.
View Article and Find Full Text PDFBrachyury co-operates with polycomb protein RYBP to regulate gastrulation and axial elongation .
Front Cell Dev Biol
November 2024
Biological Research Centre, Institute of Genetics, Hungarian Research Network, Szeged, Hungary.
Early embryonic development is a complex process where undifferentiated cells lose their pluripotency and start to gastrulate. During gastrulation, three germ layers form, giving rise to different cell lineages and organs. This process is regulated by transcription factors and epigenetic regulators, including non-canonical polycomb repressive complex 1s (ncPRC1s).
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