Endometriosis Knowledgebase


A repository for genes associated with endometriosis

Results


PMID 25820690
Gene Name HIST3H3
Condition Endometriosis
Association Associated
Sex Female
Associated genes H3K27me3, EZH2
H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis.

Reprod Sci. 2015 Sep;22(9):1134-42. doi: 10.1177/1933719115578924. Epub 2015 Mar

Colon-Caraballo, Mariano| Monteiro, Janice B| Flores, Idhaliz

Department of Microbiology, Ponce Health Sciences University-School of Medicine and Ponce Research Institute, Ponce, PR, USA.| Department of Biochemistry, Ponce Health Sciences University-School of Medicine and Ponce Research Institute, Ponce, PR, USA.

Epigenetic mechanisms may play an important role in the etiology of endometriosis. The modification of histones by methylation of lysine residues has been shown to regulate gene expression by changing chromatin structure. We have previously shown that endometriotic lesions had aberrant levels of histone acetylation (lower) and methylation (higher) than control tissues. We aimed to determine the levels of trimethylated histone 3 at lysine residue 27 (H3K27me3), a well-known repressive mark, by immunoassay of fresh tissues and immunohistochemistry (IHC) of an endometriosis-focused tissue microarray. Also, we aimed to determine levels of expression of enhancer of zeste homolog 2 (EZH2), the enzyme responsible for trimethylation of H3K27me3, in cell lines. Average levels of H3K27me3 measured by immunoassay were not significantly different in lesions compared to endometrium from patients and controls. However, there was a trend of higher levels of H3K27me3 in secretory versus proliferative endometrium. The results of IHC showed that lesions (ovarian, fallopian, and peritoneal) and secretory endometrium from controls have higher percentage of H3K27me3-positive nuclei than eutopic endometrium from patients. Endometriotic epithelial cells express high levels of EZH2, which is upregulated by progesterone. This study provides evidence in support of a role of H3K27me3 in the pathogenesis of endometriosis and for EZH2 as a potential therapeutic target for this disease, but more studies are necessary to understand the molecular mechanisms at play.

Mesh Terms: Adolescent| Adult| Blotting, Western| Cell Line| Cell Proliferation| Endometriosis/diagnosis/enzymology/*genetics| Endometrium/drug effects/*metabolism/pathology/secretion| Enhancer of Zeste Homolog 2 Protein| *Epigenesis, Genetic| Epithelial Cel