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Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas

ABSTRACT: Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas

PROVIDER: PRJNA526890 | ENA |

REPOSITORIES: ENA

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Comparison of Gene expression profiles between myometrium, MED12 mutation positive uterine leiomyomas and MED12 wildtype uterine leiomyomas

Project description:Gene expression profiles of 10 uterine leiomyomas and their matched normal myometrium specimens were studied using Affymetrix GeneChip Human Genome U133 Plus 2.0 gene expression arrays. Four tumors displayed a codon 44 mutation, four carried a intron 1 mutation, and the remaining two displayed no MED12 mutation.

2011-08-26 | GSE30673 | GEO

Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas.

Project description: Not available

| S-EPMC7040020 | biostudies-literature

Differential Expression of MED12-Associated Coding RNA 2 transcripts in Uterine Leiomyomas

Project description:The objective of this study was to elucidate the expression profile of coding RNA transcripts in leiomyomas with and without MED12 mutation and their paired myometrium.

2023-03-01 | GSE224991 | GEO

Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-01-01 | GSE128242 | GEO

MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas

Project description:Uterine leiomyoma (LM) is the most common tumor in women. Estrogen and progesterone, via their receptors ERα and PR, play essential roles in LM growth. Mediator complex subunit 12 (MED12) mutations occur in 70% of all LM and are thought to drive tumor growth in a steroid hormone-dependent manner; however, the mechanisms remain unclear. Here, we performed ChIP-seq (ERα, PR, and MED12) and RNA-seq on LM expressing mutant MED12 (mut-MED12) or wild-type MED12 and matched myometrium. Mut-MED12 altered PR and chromatin interaction landscapes, with significant PR-binding site loss in proximal promoter regions in mut-MED12 LM. Integration of cistrome and transcriptome data identified tryptophan 2,3-dioxygenase (TDO2) as a PR and MED12 target gene, which was aberrantly upregulated in mut-MED12 LM. Kynurenine, the catabolic product of TDO2, was significantly elevated in mut-MED12 LM. Tryptophan or kynurenine treatment of primary LM cells activated the aryl hydrocarbon receptor (AHR) pathway, increased cell proliferation, and inhibited apoptosis; blocking the TDO2-kynurenine-AHR pathway by siRNA knockdown or pharmacologic inhibition abolished these effects. Mut-MED12 LM cells showed higher sensitivity to these treatments. These findings suggest that activation of the TDO2-kynurenine-AHR pathway in mut-MED12 LM induces tumor growth, and may inform the development of targeted treatments and precision medicine in LM.

2023-05-01 | GSE204968 | GEO

MED12 Mutation Activates Tryptophan-Kynurenine-AHR pathway and Promotes Cell Growth in Human Uterine Leiomyoma [RNA-seq]

2023-05-01 | GSE204969 | GEO

Homo sapiens

Project description:Comparison of Gene expression profiles between myometrium, MED12 mutation positive uterine leiomyomas and MED12 wildtype uterine leiomyomas

| PRJNA144417 | ENA

Analysis of the purified RNA samples to confirm that Notch pathway activation inhibits apoptosis in uterine leiomyomas leading to fibroid growth

Project description:Uterine leiomyomas are the most common benign tumor in humans causing significant morbidity with vaginal bleeding, pelvic pressure and pain. Histologically, leiomyomas show a large degree of extracellular matrix disorganization. I am working with a colleague who recently found Notch pathway gene expression were clearly altered in fibroids (“Differential expression of the Notch signal transduction pathway: ligands, receptors and Numb in uterine leiomyomas vs. myometrium,” G. Christman, H. Tang, I. Ahmad, J. Stribley, Fertility and Sterility, Volume 88, Supp 1, S72, September 2007). Glycosaminoglycan expression was found to be over-expressed in uterine leiomyomas compared to myometrial samples (Fertility and Sterility, Vol 88 Supp 1, S106, September, 2007), but glycosyltransferase and glycosidase expression has not been reported. We have purified RNA samples from paired uterine leiomyoma and normal myometrium from a previous clinical study. Dr. Domino's laboratory hypothesis is that Notch pathway activation inhibits apoptosis in uterine leiomyomas leading to fibroid growth. Notch ligands are fucosylated glycans. The bulk of a fibroid is the extracellular matrix yet little has been studied on leiomyocyte expression of enzymes that model glycans in the extracellular matrix.

2011-04-29 | GSE28945 | GEO

Analysis of the purified RNA samples to confirm that Notch pathway activation inhibits apoptosis in uterine leiomyomas leading to fibroid growth

2011-04-29 | E-GEOD-28945 | biostudies-arrayexpress

Uterine Fibroid and Normal Myometrial Expression Profiles- U133 Arrays

Project description:Our study seeks to identify genes differentially expressed between uterine leiomyomas and normal myometrial tissue. This series consists of samples derived from normal myometrium and uterine leiomyomas obtained from fibroid afflicted patients.Total RNA was extracted from samples, converted to biotin-labeled cRNA, hybridized to oligonucleotide arrays, and followed by model based expression analysis. In order to select differentially expressed genes of interest, dChip model-based expression analysis was employed. Significant genes were identified, utilizing the dChip software, as having an average fold change of > +1.5 or < -1.5 between leiomyoma and normal myometrium and p < 0.05. Under these conditions the 226 genes in the following list were identified. Keywords: other

2003-10-17 | GSE593 | GEO

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