Project description:A series of gene expression measurements of uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene. Keywords: other
Project description:A series of gene expression measurements of normal myometrium and uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene. Keywords: other
Project description:A series of gene expression measurements of normal myometrium and uterine fibroids with mutated or wild-type fumarate hydratase (FH) gene.
Project description:Comparative proteomics on two cyanobacterial strains with the expression of either a wild-type D1 gene (OE5) or a mutated D1 gene (OE9) in Synechococcus elongatus PCC 7942.
Project description:Receptors for estrogen and progesterone frequently interact, via Cohesin/CTCF loop extrusion, at enhancers distal from regulated genes; CTCF is decreased or mutated in >20% of human endometrial tumors, indicating its importance in uterine homeostasis. To better understand how CTCF-mediated enhancer-gene interactions impact endometrial development and function, the Ctcf gene was selectively deleted in female reproductive tissues of mice. Prepubertal Ctcfd/d uterine tissue exhibited normal morphology, with a significant reduction in the number of uterine glands compared to those without Ctcf deletion (Ctcff/f mice). Post-pubertal Ctcfd/d uteri were hypoplastic with significant reduction in both the size of the endometrial stroma and number of glands. Transcriptional profiling revealed increased expression of stem cell molecules Lif, EOMES and Lgr5, and enhanced inflammation pathways following Ctcf deletion. Analysis of the response of the uterus to steroid hormone stimulation showed that the response of the uterus to estrogen was not impacted, but that CTCF deletion affects a subset of progesterone responsive genes. This finding indicates 1) mediators of P signaling remain functional following Ctcf deletion and 2) certain P regulated genes are sensitive to Ctcf deletion, suggesting they depend on gene-enhancer interactions that require CTCF. The P responsive genes altered by CTCF ablation included Ihh, Fst and Errfi1, as well as other genes involved in the regulation of critical processes including hormone response, transcription, and inhibition of tumor generation. Overall, our findings reveal that uterine Ctcf plays a key role in P dependent expression of uterine genes underlying optimal post pubertal uterine development.
Project description:Thyroid hormone receptors (TRs) mediate the genomic actions of the thyroid hormone (T3). Mutations of THRA gene cause a human disease known as resistance to thyroid hormone (RTHa). We created a mouse model expressing a dominant negative mutated TRa1 (Thra1PV/+ mice) that exhibits severely retarded growth, bone abnormalities, constipation, and anemia, as found in RTHa patients. It has been previously observed that female Thra1PV/+ mice exhibit fertility deficiency. In the present study, we aim to understand the molecular basis underlying female infertility caused by TRa1 mutants. The uterus of mutant mice atrophied with 50-60% reduction in weight, as compared with wild-type (WT) mice with reduced proliferation, increased apoptosis, and loss of ~90% of uterine glands. Fibrosis of the endometrium and squamous metaplasia were detected in the uterine epithelium of all Thra1PV/+ mice examined. RNA-seq analysis of laser-captured micro-dissected endometrium to understand the gene expression changes that lead to uterine atrophy, epithelium metaplasia, immune cells infiltration and ectopic expression of IL-33.Analysis of altered gene expression profiles has reveled by RNA-seq analysis provide new insights to understand how thyroid dysfunction could lead to female infertility.
Project description:Analysis of genes regulated by RU486 (an progesterone antagonist) in human breast cancer T47D cells and human uterine leiomyoma smooth muscle cells. The hypothesis is that RU486 inhibits tumor growth by inactivating the transcription of multiple genes which trigger critical signaling pathways to induce tumorigenesis in both breast caner and uterine leomyoma. Tissue-specific and common patterns of gene regulation may determine the therapeutic effects of antiprogestins in uterine leiomyoma and breast cancer. Keywords: Expression profiling by array
Project description:Analysis of genes regulated by RU486 (an progesterone antagonist) in human breast cancer T47D cells and human uterine leiomyoma smooth muscle cells. The hypothesis is that RU486 inhibits tumor growth by inactivating the transcription of multiple genes which trigger critical signaling pathways to induce tumorigenesis in both breast caner and uterine leomyoma. Tissue-specific and common patterns of gene regulation may determine the therapeutic effects of antiprogestins in uterine leiomyoma and breast cancer. We applied ChIP-seq to identify PR-interaction sites in T47D breast cancer cells and primary uterine leiomyoma cells treated with RU486.