title: H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis.
abstract: 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.
authors.affiliation: Department of Microbiology, Ponce Health Sciences University-School of Medicine and Ponce Research Institute, Ponce, PR, USA.
authors.forename: Mariano
authors.initials: M
authors.lastname: Colón-Caraballo
authors.affiliation: Department of Biochemistry, Ponce Health Sciences University-School of Medicine and Ponce Research Institute, Ponce, PR, USA.
authors.forename: Janice B
authors.initials: JB
authors.lastname: Monteiro
authors.affiliation: Department of Microbiology, Ponce Health Sciences University-School of Medicine and Ponce Research Institute, Ponce, PR, USA Department of Obstetrics and Gynaecology, Ponce Health Sciences University-School of Medicine and Ponce Research Institute, Ponce, PR, USA iflores@psm.edu.
authors.forename: Idhaliz
authors.initials: I
authors.lastname: Flores
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D004715:Endometriosis / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine; D008745:Methylation; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D006657:Histones; D011374:Progesterone; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D008239:Lysine
keywords: H3K27me3; endometriosis; epigenetics; histone methylation
references.citation: Mol Cancer Res. 2010 Dec;8(12):1610-8
references.pmid: 21115743
references.citation: J Cell Physiol. 2013 Apr;228(4):764-72
references.pmid: 23001792
references.citation: Epigenetics. 2012 Sep;7(9):976-81
references.pmid: 22895114
references.citation: Acta Biochim Biophys Sin (Shanghai). 2014 Oct;46(10):894-901
references.pmid: 25205219
references.citation: Cell Biochem Biophys. 2015 Jan;71(1):105-12
references.pmid: 25077680
references.citation: Med Oncol. 2013 Dec;30(4):713
references.pmid: 24132606
references.citation: PLoS Genet. 2014 Aug 07;10(8):e1004507
references.pmid: 25101834
references.citation: Chin J Physiol. 2013 Oct 31;56(5):282-90
references.pmid: 24032713
references.citation: N Engl J Med. 2009 Jan 15;360(3):268-79
references.pmid: 19144942
references.citation: Mol Cell Endocrinol. 2012 Jul 25;358(2):185-96
references.pmid: 22067514
references.citation: Fertil Steril. 2014 Mar;101(3):740-9
references.pmid: 24388204
references.citation: Mol Cancer Res. 2014 Oct;12(10):1388-97
references.pmid: 24916103
references.citation: Nat Rev Genet. 2012 Apr 03;13(5):343-57
references.pmid: 22473383
references.citation: Mol Hum Reprod. 2007 May;13(5):323-32
references.pmid: 17350963
references.citation: Am J Obstet Gynecol. 1975 May;122(2):262-3
references.pmid: 1155504
references.citation: Am J Pathol. 2001 Nov;159(5):1839-52
references.pmid: 11696444
references.citation: PLoS One. 2013 Jun 27;8(6):e68226
references.pmid: 23826380
references.citation: FASEB J. 2014 Jul;28(7):3183-96
references.pmid: 24652950
references.citation: Mol Biol Rep. 2014 Sep;41(9):5793-7
references.pmid: 24972566
references.citation: Cancer Res Treat. 2014 Jul;46(3):209-22
references.pmid: 25038756
references.citation: Circ Res. 2014 Sep 12;115(7):636-49
references.pmid: 25114098
references.citation: Clin Sci (Lond). 2014 Jan;126(2):123-38
references.pmid: 24059589
references.citation: EMBO J. 2014 Oct 1;33(19):2157-70
references.pmid: 25107471
references.citation: Cancer Cell. 2010 Aug 9;18(2):185-97
references.pmid: 20708159
references.citation: Epigenetics. 2006 Apr-Jun;1(2):106-11
references.pmid: 17965625
references.citation: Nature. 2007 Oct 11;449(7163):689-94
references.pmid: 17851529
references.citation: Eur J Obstet Gynecol Reprod Biol. 2012 May;162(1):96-101
references.pmid: 22381038
references.citation: Genomics. 2014 Feb-Mar;103(2-3):204-10
references.pmid: 24407023
references.citation: BJU Int. 2012 Feb;109(3):459-65
references.pmid: 21810159
references.citation: N Engl J Med. 2010 Jun 24;362(25):2389-98
references.pmid: 20573927
references.citation: Oncotarget. 2014 Aug 30;5(16):7172-82
references.pmid: 25115397
references.citation: Mol Hum Reprod. 2010 May;16(5):297-310
references.pmid: 20139117
references.citation: PLoS Genet. 2008 Oct;4(10):e1000242
references.pmid: 18974828
references.citation: Cell Res. 2011 Mar;21(3):381-95
references.pmid: 21321607
references.citation: Acta Biochim Biophys Sin (Shanghai). 2012 Jan;44(1):14-27
references.pmid: 22194010
references.citation: Reprod Sci. 2014 Mar;21(3):305-18
references.pmid: 23899551
references.citation: Mol Hum Reprod. 2009 Oct;15(10):587-607
references.pmid: 19651637
references.citation: BJU Int. 2016 Feb;117(2):351-62
references.pmid: 24612432
references.citation: Mol Endocrinol. 2011 Nov;25(11):1892-903
references.pmid: 21903722
references.citation: Cancer Prev Res (Phila). 2012 Mar;5(3):484-91
references.pmid: 22144423
references.citation: Oncogene. 2008 Dec 11;27(58):7274-84
references.pmid: 18806826
references.citation: Reprod Sci. 2012 May;19(5):483-92
references.pmid: 22344732
references.citation: Acta Neuropathol. 2014 Nov;128(5):743-53
references.pmid: 25200322
references.citation: Fertil Steril. 2012 Sep;98(3):511-9
references.pmid: 22819144