Histone post-translational modifications modulate gene expression through epigenetic gene regulation. The core histone H3 family members, H3.1, H3.2, and H3.3, play a central role in epigenetics. H3 histones can acquire many post-translational modifications, including the trimethylation of H3K27 (H3K27me3), which represses transcription. Triple methylation of H3K27 is performed by the histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2), a component of the Polycomb Repressive Complex 2. Both global increases and decreases in H3K27me3 have been implicated in a wide range of cancer types. Here, we explore how opposing changes in H3K27me3 contribute to cancer by highlighting its role in two vastly different cancer types; (1) a form of glioma known as diffuse midline glioma H3K27-altered and (2) epithelial ovarian cancer. These two cancers vary widely in the age of onset, sex, associated mutations, and cell and organ type. However, both diffuse midline glioma and ovarian cancer have dysregulation of H3K27 methylation, triggering changes to the cancer cell transcriptome. In diffuse midline glioma, the loss of H3K27 methylation is a primary driving factor in tumorigenesis that promotes glial cell stemness and silences tumor suppressor genes. Conversely, hypermethylation of H3K27 occurs in late-stage epithelial ovarian cancer, which promotes tumor vascularization and tumor cell migration. By using each cancer type as a case study, this review emphasizes the importance of H3K27me3 in cancer while demonstrating that the mechanisms of histone H3 modification and subsequent gene expression changes are not a one-size-fits-all across cancer types.
Bibliographical noteFunding Information:
This work was funded by the Mayo Clinic/NIH training grant 5-T32-CA217836-02 (CAD), the United States Department of Defense CA200707 (EHH), NIH R01 NS417132 (EHH), Minnesota Partnership for Biotechnology and Medical Genomics Collaborative Research Grant MNP 19.11 (EHH), the American Cancer Society ACS RSG-17-230-01-TBG (JPR) and the United States Department of Defense W81XWH-22-1-1045 (JPR).
© 2022 by the authors.
- diffuse intrinsic pontine glioma
- diffuse midline glioma
- epithelial ovarian cancer
- histone H3
PubMed: MeSH publication types
- Journal Article
- Research Support, U.S. Gov't, Non-P.H.S.
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Extramural