H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis

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 his...

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Bibliographic Details
Published in:Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2015-09, Vol.22 (9), p.1134-1142
Main Authors: Colón-Caraballo, Mariano, Monteiro, Janice B., Flores, Idhaliz
Format: Article
Language:English
Subjects:
Adolescent
Adult
Blotting, Western
Cell Line
Cell Proliferation
Embryology
Endometriosis - diagnosis
Endometriosis - enzymology
Endometriosis - genetics
Endometrium - drug effects
Endometrium - metabolism
Endometrium - pathology
Enhancer of Zeste Homolog 2 Protein
Epigenesis, Genetic
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial Cells - pathology
Female
Histones - metabolism
Humans
Immunohistochemistry
Lysine
Medicine & Public Health
Methylation
Middle Aged
Obstetrics/Perinatology/Midwifery
Original
Original Article
Polycomb Repressive Complex 2 - metabolism
Progesterone - pharmacology
Protein Processing, Post-Translational
Reproductive Medicine
Tissue Array Analysis
Young Adult
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Summary: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.
ISSN:1933-7191
1933-7205
DOI:10.1177/1933719115578924