Genes Downregulated in Endometriosis Are Located Near the Known Imprinting Genes

Kobayashi, Hiroshi; Higashiura, Yumi; Koike, Nobuyuki; Akasaka, Juria; Uekuri, Chiharu; Iwai, Kana; Niiro, Emiko; Morioka, Shigefumi; Yamada, Yoshiaki

doi:10.1177/1933719114526473

Cited by 10 publications

(11 citation statements)

References 90 publications

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“…Consistent with this hypothesis, enhanced estrogenic activity and reduced progesterone responsiveness are considered to be involved in the etiology of endometriosis (11). Therefore, endometriosis is a chronic disease with substantial epigenetic dysregulation of decidualization susceptibility genes (4).…”

Section: Discussionmentioning

confidence: 90%

“…To date, two studies investigating this context have been published (4,38). Firstly, the presence of hypermethylated regions located at the ends of chromosomes among endometriosis samples suggested that the distribution pattern of the hypermethylation was not random (38).…”

Section: Mechanistic Link Between Genomic Imprinting and Endometriosimentioning

confidence: 99%

“…This indicated that altered non-random methylation of CpG sites which do not carry the mutation has a possible role in the development of endometriosis. Secondly, among the 29 hypermethylated genes in endometriosis, 19 genes (65.5%) were located near the known imprinted foci (4). Genes designated to genomic imprinting are associated with allele-specific expression.…”

Section: Mechanistic Link Between Genomic Imprinting and Endometriosimentioning

confidence: 99%

“…Epidemiological studies have suggested that gene polymorphism of estrogen and progesterone receptors is associated with a risk of endometriosis (2,3). Furthermore, several studies have been designed to identify candidate genes and their pathways of endometriosis susceptibility (4,5). In line with those of earlier studies, the results showed that the candidate pathways, which included genes with functions as hormonal regulators, cell cycle regulators, signal transducers, transcription factors, hormones, cytokines, chemokines and (pro)inflammatory molecules, proteases, as well as molecules with functions in cell adhesion, motility, stress response, detoxification, immune response and metabolism, may be associated with susceptibility to endometriosis (4,5).…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic dysregulation of endometriosis susceptibility genes (Review)

Koike¹,

Higashiura²,

Akasaka³

et al. 2015

Molecular Medicine Reports

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The aim of the present review was to illustrate how dysregulation of hormonal signaling regulates expressional changes of spatially associated genes in endometriosis. From a multi‑platform endometriosis dataset, an integrated analysis was performed of epigenomic changes of several biologically relevant genes that have been validated in the literature. Estrogen receptor (ER) may act as a direct epigenetic driver for endometriosis establishment, maintenance and progression. A majority of endometriosis susceptibility genes may be present in functional downstream targets of ER and located near the known imprinting genes. Previous studies have shed light on the overlapping genetic signatures between endometriosis development and the defective decidualization process. The steroid hormone‑mediated decidualization signaling pathway was shown to be frequently dysregulated in endometriosis. DNA methylation is associated with various intragenic or intergenic epigenetic modifications of chromatin. Chromatin architecture may be established in temporal and spatial orchestration of the recruitment of genes specifically downregulated in endometriosis. In conclusion, defective chromatin architecture at the ER target locus may have a key role in endometriosis. Endometriosis represents an interesting model to explore the variation of expression of spatially associated genes.

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Section: Discussionmentioning

confidence: 90%

Section: Mechanistic Link Between Genomic Imprinting and Endometriosimentioning

confidence: 99%

Section: Mechanistic Link Between Genomic Imprinting and Endometriosimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic dysregulation of endometriosis susceptibility genes (Review)

Koike¹,

Higashiura²,

Akasaka³

et al. 2015

Molecular Medicine Reports

Self Cite

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“…Genomic imprinting; DNA methylation; histone modifications with different nominations (acetylation/ histone phosphorylation/histone ubiquitylation/ histone sumoylation); microRNAs [183] and recently discovered, stranded, noncoding RNAs (ncRNAs) [168]; transcription factor network; and chromatin remodeling are known to regulate transcription of target genes. Genomic imprinting is an epigenetic phenomenon known to regulate DNA methylation of either maternal or paternal alleles [184], and the male and female germ lines guide the allele-specific DNA methylation marking and histone modification onto specific gene regions of parental alleles [185]. The epigenome, the collection of DNA methylation, and the histone modifications can be influenced by environmental factors.…”

Section: Epigenetics In Endometriosis: Methylation Pattern Of Sexual mentioning

confidence: 99%

Progesterone Resistance and Adult Stem Cells’ Genomic and Epigenetic Changes in the Puzzle of Endometriosis

Russu¹

2019

Molecular Bases of Endometriosis - The Integration Between Research and Clinical Practice

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Endometriosis is a chronic inflammatory disease under hormonal/nonhormonal regulation, and microenvironment influences, originating in adult stem cells (mainly of bone marrow/endometrial progenitor mesenchymal type), and their exosomes, with special migratory and adhesion capacities. The postmenstrual repair with regeneration of eutopic and ectopic endometrium has similar genetic and epigenetic changes versus disease-free women. The competition between ectopic and eutopic endometrium for a limited supply of stem cells, and the depletion of normal stem cells flux to the uterus is considered the novel mechanism through which endometriosis interferes with endometrial functions and fertility. The gene expression DNA/RNA or microRNA changes/dysregulation of estrogen and progesterone receptors represent a possible explanation of progesterone resistance or loss of progesterone signalling in ectopic, and eutopic endometrium versus normal. The genes' changes involved in hormonal/non-hormonal pathways control of eutopic/ectopic endometrial cells, and of invaded tissues/organs may explain the disease persistency, progression and severity. Deficient DNA methylation of ERβ, the initial genomic event is followed by pathologic over-expressed ERβ in ectopic stromal cells, and it dictates the decline of PR isoforms, PRB being significantly lower in ectopic and eutopic endometrium. Altered expression of ERα, ERβ, and PRs accompanies the conversion of resident normal endometrial cells to ectopic lesions.

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Endometriosis, endocrine disrupters, and epigenetics: an investigation into the complex interplay in women with polybrominated biphenyl exposure and endometriosis

Gerkowicz

Curtis

Knight

et al. 2020

J Assist Reprod Genet

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Purpose Endocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to polybrominated biphenyl (PBB). Methods Cross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the β value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings. Results In total, 39,877 CpGs nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity, although none remained significant after correction for multiple comparisons (FDR < 0.05). Pathway analysis of these CpGs showed enrichment in 68 biologic pathways involved in various endocrine, immunologic, oncologic, and cell regulation processes as well as embryologic reproductive tract development and function (FoxO, Wnt, and Hedgehog signaling). We identified 42,261 CpG sites in the literature reported to be associated with endometriosis; 2012 of these CpG sites were also significant in our cohort. Conclusion We found 39,877 CpG sites that nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity; however, none remained significant after correction for multiple comparisons (FDR < 0.05).

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Genes Downregulated in Endometriosis Are Located Near the Known Imprinting Genes

Cited by 10 publications

References 90 publications

Epigenetic dysregulation of endometriosis susceptibility genes (Review)

Epigenetic dysregulation of endometriosis susceptibility genes (Review)

Progesterone Resistance and Adult Stem Cells’ Genomic and Epigenetic Changes in the Puzzle of Endometriosis

Endometriosis, endocrine disrupters, and epigenetics: an investigation into the complex interplay in women with polybrominated biphenyl exposure and endometriosis

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