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Genome-wide chromatin interaction maps of enhancer-promoter and promoter-promoter contacts in 5 leiomyoma (MED12 G44 mutant) and 5 matched normal myometrium (WT) patient tissue samples.

ABSTRACT: Genome-wide chromatin interaction maps of enhancer-promoter and promoter-promoter contacts in 5 leiomyoma (MED12 G44 mutant) and 5 matched normal myometrium (WT) patient tissue samples.

PROVIDER: PRJNA526866 | ENA |

REPOSITORIES: ENA

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Profiling of Myometrium and Leiomyoma transcriptomes in 15 leiomyoma (MED12 G44 mutant) and 15 matched normal myometrium (WT) patient tissue samples.

Project description:Through comprehensive profiling of transcribed genes in myometrium and leiomyoma tissue samples, we demonstrate two distinct gene expression profiles for myometrium and leiomyoma. This study shows that transcriptional dysregulation, and not post-transcriptional dysregulation, is primarily responsible for the perturbations of key biological processes in leiomyomas such as the extracellular matrix organization.

2020-01-01 | GSE128229 | GEO

Profiling of Myometrium and Leiomyoma transcriptomes in 15 leiomyoma (MED12 G44 mutant) and 15 matched normal myometrium (WT) patient tissue samples.

Project description:Profiling of Myometrium and Leiomyoma transcriptomes in 15 leiomyoma (MED12 G44 mutant) and 15 matched normal myometrium (WT) patient tissue samples.

| PRJNA526865 | ENA

Epigenome analysis of uterin leiomyoma and myometrium with or without leiomyoma [Methylation data]

Project description:Profiles of genome-wide DNA methylation were investigated in leiomyomas and in myometrium with and without leiomyomas. Profiles of DNA methylation in the myometrium with and without leiomyomas were quite similar while those in leiomyomas were distinct. Bisulphite converted DNA from the three uterine leiomyoma, three myometrium with leiomyoma and three myometrium without leiomyoma were hybridised to the Illumina infinium HumanMethylation450 BeadChip.

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

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.

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

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