Project description:Profiles of PGR genome occupancy in human myometrial specimens were documented by ChIP-seq to investigate downstream targets of the progesterone receptor and candidate partner transcription regulators at the nonpregnant and term pregnant stages.
Project description:The myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were subject to RNAseq, ATAC-seq and PGR ChIP-seq assays to profile transcriptome, assessible genome and PGR occupancy.
Project description:Progesterone signaling is crucial for pregnancy. To investigate the role of myometrial progesterone receptor in support of pregnancy, genome-wide gene expression profiles of pregnant uterine tissues from myometrial PGR knockout and control mice were profiled by RNAseq. The transcriptomic alterations in response to PGR loss permit identification of the underlying molecular mechanisms by which progesterone and PGR control myometrial homeostasis for pregnancy.
Project description:Progesterone signaling is crucial for pregnancy. To investigate the role of myometrial progesterone receptor in support of pregnancy, genome-wide gene expression profiles of pregnant uterine tissues from myometrial PGR knockout and control mice were profiled by RNAseq. The transcriptomic alterations in response to PGR loss permit identification of the underlying molecular mechanisms by which progesterone and PGR control myometrial homeostasis for pregnancy.
Project description:The open chromatin regions of nonpregnant and term pregnant human myometrial tissues were assessed by ATAC-seq to gain insight on potential genome regulatory elements in vivo. patterns of accessible genome change between NP and TP myometrium, leading to altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors and MEF2A transcription factors.
Project description:The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were used for genome-wide analyses to elucidate potential future preventive or therapeutic targets involved in the regulation of labor. Using myometrial tissues directly subjected to RNA sequencing (RNA-seq), progesterone receptor (PGR) chromatin immunoprecipitation sequencing (ChIP-seq), and histone modification ChIP-seq, we profiled genome-wide changes associated with gene expression in myometrial smooth muscle tissue in vivo. In TIL myometrium, PGR occupied predominatly promoter regions including the classical progesterone response element, whereas it bound predominantly to intergenic regions in TNIL myometrial tissue. Differential binding analysis uncovered over 1700 differential PGR-bound sites between TIL and TNIL with 1361 sites gained and 428 lost in labor. Functional analysis identified multiple pathways involved in cAMP-mediated signaling enriched in labor. A three-way integration of the data for ChIP-seq, RNA-seq and active histone marks uncovered the following genes associated with PGR binding, transcriptional activation and altered mRNA levels: ATP11A, CBX7, and TNS1. In vitro studies showed that ATP11A, CBX7, and TNS1 are progesterone responsive. We speculate that these genes may contribute to the contractile phenotype of the myometrium during various stages of labor. In conclusion, we provide novel labor associated genome-wide events and PGR-target genes that can serve as targets for future mechanistic studies.
Project description:The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were used for genome-wide analyses to elucidate potential future preventive or therapeutic targets involved in the regulation of labor. Using myometrial tissues directly subjected to RNA sequencing (RNA-seq), progesterone receptor (PGR) chromatin immunoprecipitation sequencing (ChIP-seq), and histone modification ChIP-seq, we profiled genome-wide changes associated with gene expression in myometrial smooth muscle tissue in vivo. In TIL myometrium, PGR occupied predominatly promoter regions including the classical progesterone response element, whereas it bound predominantly to intergenic regions in TNIL myometrial tissue. Differential binding analysis uncovered over 1700 differential PGR-bound sites between TIL and TNIL with 1361 sites gained and 428 lost in labor. Functional analysis identified multiple pathways involved in cAMP-mediated signaling enriched in labor. A three-way integration of the data for ChIP-seq, RNA-seq and active histone marks uncovered the following genes associated with PGR binding, transcriptional activation and altered mRNA levels: ATP11A, CBX7, and TNS1. In vitro studies showed that ATP11A, CBX7, and TNS1 are progesterone responsive. We speculate that these genes may contribute to the contractile phenotype of the myometrium during various stages of labor. In conclusion, we provide novel labor associated genome-wide events and PGR-target genes that can serve as targets for future mechanistic studies.
Project description:PGR genome occupancy and H3K27ac histone mark profiles in pregnant mouse uterine specimens were documented by ChIP-seq to investigate downstream targets of the progesterone receptor and candidate partner transcription regulators.