The Epigenetics of Endometriosis

Guo, Sun‐Wei

doi:10.1016/b978-0-12-388415-2.00022-6

Cited by 17 publications

(28 citation statements)

References 199 publications

(136 reference statements)

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“…2,21,22 It is well known that promoter regions of endometriosis candidate genes such as HOXA10, CDH1, and PGR are hypermethylated contributing to defects in uterine receptivity, invasiveness of endometrial cells, and progesterone resistance, respectively. 23 DNA methylation is known to work together with histone modifications to regulate gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…1 Knowledge of the pathophysiology of endometriosis is limited, but genetic, environmental, inflammatory, and, recently, epigenetic factors are known to be involved in this disease. [2][3][4][5] Epigenetic mechanisms exert their biological effects by regulating gene expression via modulation of chromatin structure without affecting the nucleotide sequence. Several epigenetic mechanisms regulate gene expression including promoter methylation at CpG islands and distinct histone modifications including acetylation, methylation, phosphorylation, and sumoylation.…”

Section: Introductionmentioning

confidence: 99%

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H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis

2015

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis

2015

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“…Aberrant patterns of histone protein acetylation, DNA methylation, and the deregulation of micro RNA expression are mechanisms that have been implicated in endometriosis. 5 Histone deacetylases (HDACs) are a family of enzymes that mainly modulate the acetylation status of histones. The HDACs play a crucial role in gene regulation by reversing histone acetylation, which causes a condensation of chromosomal DNA and consequently reduces gene transcription.…”

Section: Introductionmentioning

confidence: 99%

The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

et al. 2013

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Class I histone deacetylases (HDACs-1-3) play an important role in steroid hormone-dependent gene expression and in modulating cell survival and proliferation. We analyzed their expression in a tissue microarray including 74 endometriosis samples and 30 normal endometrium controls. The mean HDAC-1 immunoreactivity score (IRS + standard deviation) was 7.6 + 2.5 in endometriosis and 5.3 + 2.3 in normal endometrium (P < .001). In contrast, the IRSs of HDAC-2 and -3 were 11.7 + 0.7 and 11.8 + 1.1 in endometriosis and 11.6 + 1.0 and 11.9 + 0.4 in normal endometrium (P ¼ .7 and P ¼ .2), respectively. Significant correlations were found between HDAC-1 and estrogen (-alpha/-beta) and progesterone receptor expression. In conclusion, HDAC-1, but not HDAC-2/-3, was significantly increased in endometriosis and associated with steroid hormone receptor expression that may reflect interdependence. In context with the literature, specific inhibitors of HDAC-1 may have inhibitory activities similar to those of broad-spectrum HDAC inhibitors and may be clinically tolerated, which would increase their chance as an option in the treatment of endometriosis.

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“…Ezen túlmenően az immunrendszer és az endometrium által nagyobb mennyiségben termelt gyulladásos citokinek, illetve növekedési faktorok kedveznek az ectopiás endometriumszigetek beágyazódásának és növekedésének. A Sawalha és kutatócsoportja által 2008-ben publikált közlemény az endometriosis hátte-rében zajló immunológiai változásokra ható epigenetikai mechanizmusok létezése mellett érvel; ezt további kutatási eredmények erősítik meg, elég csak az antigénpre-zentáció, T-sejt-differenciálódás vagy éppen a citokintermelés epigenetikai hátterére utalni [34,35].…”

Section: Epigenetikai Mechanizmusok Az Endometriosis Kialakulásának Hunclassified

“…Később újabb cél-pontgéneket sikerült azonosítani, amelyek működését bizonyos miRNS-ek befolyásolni képesek. Ezek közül a DNMT3A enzim a DNS-metilációban játszott szerepe miatt az epigenetikai szabályozómechanizmusok egyik ismert szereplője [35].…”

Section: Epigenetikai Mechanizmusok Az Endometriosis Kialakulásának Hunclassified

Epigenetic background of the most common non-oncologic gynecological diseases

et al. 2014

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Az epigenetikai mechanizmusok az alapvető életfolyamatok irányításában részt vevő gének működésére gyakorolnak hatást. E környezeti tényezők némelyike képes a génműködés megváltoztatására vagy kiiktatására. A környezet génaktivitásra gyakorolt, örökölhető fenotípus-változásokat eredményező hatásai a kromatinban úgynevezett epigenetikus jelzéseket hoznak létre, amelyek a DNS kémiai módosulását okozzák. A szülészet-nőgyógyászatban számos olyan terhespatológiai, onkológiai és nem daganatos nőgyógyászati kórkép van, amelyek kialakulásában az epigenetikai mechanizmusok fontos szerepet játszanak. A leiomyoma uteri számos etiológiai tényező együttállása esetén alakul ki, ezért hátterében egy feltehetően komplexebb epigenetikai szabályozórendszer jelenléte valószínűsíthető. Az endometriosis multifaktoriális kóreredete immunológiai és hormonális kóroki tényezők szerepét valószínűsíti. Ezek hatásmechanizmusának minél részletesebb génszintű ismerete jelent(ene) lehetőséget az érvényre jutó epigenetikai mechanizmusok azonosítására, illetve -a későbbiekben -hatásuk kiküszöbölésére. A polycystás ovarium szindróma vonatkozásában az epigenetikai kutatások irányát meghatározza a valószínűsíthető in utero eredet, amely mind a prekoncepcionális, mind a terhesgondozás során a megelőzés és a kezelés lehetőségeit kínálhatja. Orv. Hetil., 2014, 155(13), 492-499. Kulcsszavak: epigenetika, DNS-metiláció, endometriosis, PCOS, leiomyoma uteri, miRNS Epigenetic background of the most common non-oncologic gynecological diseasesEpigenetic effects infl uence the function of genes regulating the main physiological mechanisms. Some of these environmental factors may reduce or inhibit the function of these genes. The environmental effects on gene function may result in a change of the DNA structure leading to non-heritable phenotype changes. Epigenetic factors play an important etiological role in the development of numerous diseases in obstetrics and gynecology. Uterine fi broids probably have a complex etiological background including epigenetic mechanisms. The multifactorial aetiology of endometriosis suggests key roles for immunological and hormonal factors in the development of the diseases. These mechanisms are infl uenced by epigenetic factors, which may serve as therapeutic targets in the future. The possible in utero origin of polycystic ovary syndrome determines the main directions of research concerning epigenetic factors in the etiological background, with the hope of eventual prevention and/or treatment in the preconceptional period as well as during pregnancy care.

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The Epigenetics of Endometriosis

Cited by 17 publications

References 199 publications

H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis

H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis

The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

Epigenetic background of the most common non-oncologic gynecological diseases

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