scholarly journals A Genomic Approach to Identify Novel Progesterone Receptor Regulated Pathways in the Uterus during Implantation

2002 ◽  
Vol 16 (12) ◽  
pp. 2853-2871 ◽  
Author(s):  
Yong-Pil Cheon ◽  
Quanxi Li ◽  
Xueping Xu ◽  
Francesco J. DeMayo ◽  
Indrani C. Bagchi ◽  
...  
Keyword(s):  
Gene Networks ◽  
Time Course ◽  
Target Genes ◽  
Reproductive Tract ◽  
Cell Types ◽  
Temporal Analysis ◽  
Pregnant Mouse ◽  
Initial Examination ◽  
Mouse Uterus ◽  
Pregnant Uterus

Abstract The cellular actions of steroid hormone progesterone (P) are mediated via its nuclear receptors, which regulate the expression of specific target genes. The identity of gene networks that are regulated by the P receptors (PRs) in the uterus at various stages of the reproductive cycle and pregnancy, however, remain largely unknown. In this study, we have used oligonucleotide microarrays to identify mRNAs whose expression in the pregnant mouse uterus is modulated by RU486, a well-characterized PR antagonist, which is also an effective inhibitor of implantation. We found that, in response to RU486, expression of mRNAs corresponding to 78 known genes was down-regulated at least 2-fold in the preimplantation mouse uterus. The PR regulation of several of these genes was ascertained by administering P to ovariectomized wild-type and PR knockout (PRKO) mice. Detailed spatio-temporal analysis of these genes in the pregnant uterus indicated that their expression in the epithelium and stroma could be correlated with the expression of PR in those cell types. Furthermore, time-course studies suggested that many of these genes are likely primary targets of PR regulation. We also identified 70 known genes that were up-regulated at least 2-fold in the pregnant uterus in response to RU486. Interestingly, initial examination of a number of RU486-inducible genes reveals that their uterine expression is also regulated by estrogen. The identification of several novel PR-regulated gene pathways in the reproductive tract is an important step toward understanding how P regulates the physiological events leading to implantation.

scholarly journals Annotation of Chromatin States in 66 Complete Mouse Epigenomes During Development

2020 ◽  
Author(s):  
Arjan van der Velde ◽  
Kaili Fan ◽  
Junko Tsuji ◽  
Jill Moore ◽  
Michael Purcaro ◽  
...  
Keyword(s):  
Time Course ◽  
Target Genes ◽  
Cell Types ◽  
Developmental Time ◽  
Developmental Trajectory ◽  
Phase Iii ◽  
Chromatin State ◽  
Mammalian Development ◽  
Chromatin States ◽  
Transcription Start Sites

ABSTRACTThe morphologically and functionally distinct cell types of a multicellular organism are maintained by epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 10.5 to birth. Applying the ChromHMM algorithm to these epigenomes, we annotated eighteen chromatin states with characteristics of promoters, enhancers, transcribed regions, repressed regions, and quiescent regions throughout the developmental time course. Our integrative analyses delineate the tissue specificity and developmental trajectory of the loci in these chromatin states. Approximately 0.3% of each epigenome is assigned to a bivalent chromatin state, which harbors both active marks and the repressive mark H3K27me3. Highly evolutionarily conserved, these loci are enriched in silencers bound by Polycomb Repressive Complex proteins and the transcription start sites of their silenced target genes. This collection of chromatin state assignments provides a useful resource for studying mammalian development.

scholarly journals β-Catenin (CTNNB1) in the Mouse Uterus During Decidualization and the Potential Role of Two Pathways in Regulating Its Degradation

2007 ◽  
Vol 55 (9) ◽  
pp. 963-974 ◽  
Author(s):  
Jennifer L. Herington ◽  
JiaJia Bi ◽  
John D. Martin ◽  
Brent M. Bany
Keyword(s):  
Binding Protein ◽  
E3 Ligase ◽  
Progressive Increase ◽  
Pregnant Mouse ◽  
Transcriptional Coactivator ◽  
Mouse Uterus ◽  
Endometrial Stromal Cells ◽  
Pregnant Uterus ◽  
Steady State Levels

β-catenin plays a role in cell adhesion and as a transcriptional coactivator. Its levels are regulated in cells by controlling its degradation through ubiquitination by two different E3 ligase complexes. One complex contains β-transducing repeat containing (BTRC) protein, which binds to β-catenin when phosphorylated on specific (S33 and S37) residues, whereas the other involves calcyclin-binding protein (CACYBP). The aim of this study was to determine the localization and levels of total and active (S33/S37-dephosphorylated) β-catenin in the pregnant mouse uteri and those undergoing artificially stimulated decidualization. These two forms of β-catenin were localized almost exclusively to the endometrial epithelia just prior to the onset of implantation. Although this localization continued after the onset of implantation, there were less epithelial cells present in areas of the uterus undergoing decidualization. Rather, there was a progressive increase in β-catenin localization in endometrial stromal cells undergoing decidualization in the anti-mesometrial and, to a lesser extent, in the mesometrial regions. The presence of a conceptus was not required for the changes in localization seen in the pregnant uterus because similar findings were also seen in uteri undergoing artificially stimulated decidualization. Finally, overall levels of total, active (S33 and S37 dephosphorylated), and phosphorylated (S33/S37/T42) β-catenin protein and the steady-state levels of calcyclin-binding protein mRNA changed in the uterus during decidualization. The result of this study shows the changing localization and levels of β-catenin in the mouse uterus during decidualization. Further, the results suggest potential roles for both the BTRC and CACYBP E3 ligase mechanisms of β-catenin ubiquitination in the uterus during decidualization.

scholarly journals IMMUNOFLUORESCENT STUDIES OF THE HISTOPATHOGENESIS OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTION

1964 ◽  
Vol 120 (5) ◽  
pp. 829-840 ◽  
Author(s):  
Roger E. Wilsnack ◽  
Wallace P. Rowe
Keyword(s):  
Liver Parenchyma ◽  
Cell Types ◽  
Pregnant Mouse ◽  
Virus Antigen ◽  
Lymphocytic Choriomeningitis ◽  
Alveolar Cells ◽  
Pregnant Uterus ◽  
Mouse Tissues ◽  
Lymphocytic Choriomeningitis Virus Infection ◽  
Almost All

LCM virus antigen was visualized in infected tissue cultures and mouse tissues by the direct immunofluorescent procedure. In all instances, antigen was localized to the cytoplasm. In intracerebrally infected mice, antigen was almost completely restricted to meninges, choroid plexus, and ependyma; at no time were neurons involved. Mice infected by intraperitoneal inoculation of a viscerotropic strain demonstrated antigen chiefly in liver parenchyma, splenic reticulum, bronchi, and alveolar cells. Congenitally infected mice showed antigen in almost all cell types observed, but generally in only a minority of cells; infection was often focal in distribution. Liver, kidney, pregnant uterus, and trophoblast were most extensively involved. No antigen was observable in ova of a pregnant mouse.

scholarly journals A cDNA cloned from pregnant mouse uterus exhibits temporo-spatial expression and predicts a novel protein

1998 ◽  
Vol 330 (2) ◽  
pp. 947-950 ◽  
Author(s):  
W. John KASIK
Keyword(s):  
Late Pregnancy ◽  
Pregnant Mouse ◽  
Open Reading Frame ◽  
Mouse Uterus ◽  
Pregnant Uterus ◽  
Reading Frame ◽  
Spatial Expression ◽  
Conceptual Translation ◽  
Novel Protein ◽  
Specific Mrna

A cDNA was cloned from a pregnant mouse uterus cDNA library. On conceptual translation, the cDNA has one long open reading frame that predicts a novel protein of 606 amino acids. This protein is principally composed of two CUB domains and a ZP domain; motifs found in proteins implicated in egg-sperm recognition. Probes derived from the cDNA were used to conduct Northern hybridizations. The expression of this mRNA is temporal; message first appears in the uterus 6 days prior to birth, it increases each subsequent day to attain maximal levels at 3 days prior to birth and then abruptly decreases during the last 3 days of pregnancy. The expression of this mRNA is restricted; message is abundant in the uterus during late pregnancy, but it is not found in non-pregnant uterus or in a variety of adult or fetal tissues. The temporo-spatial expression of this pregnant uterus specific mRNA and the consolidation in the predicted protein of two motifs implicated in early pregnancy events suggests that the product of the gene represented by this mRNA may play an important role in events that transpire during late pregnancy.

scholarly journals Deletion of Dicer in Somatic Cells of the Female Reproductive Tract Causes Sterility

2008 ◽  
Vol 22 (10) ◽  
pp. 2336-2352 ◽  
Author(s):  
Ankur K. Nagaraja ◽  
Claudia Andreu-Vieyra ◽  
Heather L. Franco ◽  
Lang Ma ◽  
Ruihong Chen ◽  
...  
Keyword(s):  
Target Genes ◽  
Reproductive Tract ◽  
Somatic Cells ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Conditional Knockout ◽  
Female Sterility ◽  
Small Interfering Rnas ◽  
Conditional Deletion ◽  
And Function

Abstract Dicer is an evolutionarily conserved ribonuclease III that is necessary for microRNA (miRNA) processing and the synthesis of small interfering RNAs from long double-stranded RNA. Although it has been shown that Dicer plays important roles in the mammalian germline and early embryogenesis, the functions of Dicer-dependent pathways in the somatic cells of the female reproductive tract are unknown. Using a transgenic line in which Cre recombinase is driven by the anti-Müllerian hormone receptor type 2 promoter, we conditionally inactivated Dicer1 in the mesenchyme of the developing Müllerian ducts and postnatally in ovarian granulosa cells and mesenchyme-derived cells of the oviducts and uterus. Deletion of Dicer in these cell types results in female sterility and multiple reproductive defects including decreased ovulation rates, compromised oocyte and embryo integrity, prominent bilateral paratubal (oviductal) cysts, and shorter uterine horns. The paratubal cysts act as a reservoir for spermatozoa and oocytes and prevent embryos from transiting the oviductal isthmus and passing the uterotubal junction to enter the uterus for implantation. Deep sequencing of small RNAs in oviduct revealed down-regulation of specific miRNAs in Dicer conditional knockout females compared with wild type. The majority of these differentially expressed miRNAs are predicted to regulate genes important for Müllerian duct differentiation and mesenchyme-derived structures, and several of these putative target genes were significantly up-regulated upon conditional deletion of Dicer1. Thus, our findings reveal diverse and critical roles for Dicer and its miRNA products in the development and function of the female reproductive tract.

scholarly journals Annotation of chromatin states in 66 complete mouse epigenomes during development

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Arjan van der Velde ◽  
Kaili Fan ◽  
Junko Tsuji ◽  
Jill E. Moore ◽  
Michael J. Purcaro ◽  
...  
Keyword(s):  
Target Genes ◽  
Cell Types ◽  
Developmental Trajectory ◽  
Phase Iii ◽  
Chromatin State ◽  
Mammalian Development ◽  
Chromatin States ◽  
Transcription Start Sites ◽  
Repressive Mark ◽  
Distinct Cell

AbstractThe morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 11.5 to birth. Applying the ChromHMM algorithm to these epigenomes, we annotated eighteen chromatin states with characteristics of promoters, enhancers, transcribed regions, repressed regions, and quiescent regions. Our integrative analyses delineate the tissue specificity and developmental trajectory of the loci in these chromatin states. Approximately 0.3% of each epigenome is assigned to a bivalent chromatin state, which harbors both active marks and the repressive mark H3K27me3. Highly evolutionarily conserved, these loci are enriched in silencers bound by polycomb repressive complex proteins, and the transcription start sites of their silenced target genes. This collection of chromatin state assignments provides a useful resource for studying mammalian development.

scholarly journals Thyroid Hormone Action in Cerebellum and Cerebral Cortex Development

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Fabrice Chatonnet ◽  
Frédéric Picou ◽  
Teddy Fauquier ◽  
Frédéric Flamant
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Glial Cell ◽  
Nuclear Receptors ◽  
Target Genes ◽  
Cell Types ◽  
Hormone Action ◽  
Cerebral Cortex Development ◽  
Thyroid Hormone Action

Thyroid hormones (TH, including the prohormone thyroxine (T4) and its active deiodinated derivative 3,,5-triiodo-L-thyronine (T3)) are important regulators of vertebrates neurodevelopment. Specific transporters and deiodinases are required to ensure T3 access to the developing brain. T3 activates a number of differentiation processes in neuronal and glial cell types by binding to nuclear receptors, acting directly on transcription. Only few T3 target genes are currently known. Deeper investigations are urgently needed, considering that some chemicals present in food are believed to interfere with T3 signaling with putative neurotoxic consequences.

scholarly journals Heparan Sulfate Proteoglycan Sulfation Regulates Uterine Differentiation and Signaling During Embryo Implantation

Endocrinology ◽  
2018 ◽  
Vol 159 (6) ◽  
pp. 2459-2472 ◽  
Author(s):  
Yan Yin ◽  
Adam Wang ◽  
Li Feng ◽  
Yu Wang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Heparan Sulfate ◽  
Signaling Pathways ◽  
Reproductive Tract ◽  
Ovarian Function ◽  
Embryo Implantation ◽  
Uterine Epithelium ◽  
Female Reproductive Tract ◽  
Uterine Receptivity ◽  
Mouse Uterus

Abstract To prepare for embryo implantation, the uterus must undergo a series of reciprocal interactions between the uterine epithelium and the underlying stroma, which are orchestrated by ovarian hormones. During this process, multiple signaling pathways are activated to direct cell proliferation and differentiation, which render the uterus receptive to the implanting blastocysts. One important modulator of these signaling pathways is the cell surface and extracellular matrix macromolecules, heparan sulfate proteoglycans (HSPGs). HSPGs play crucial roles in signal transduction by regulating morphogen transport and ligand binding. In this study, we examine the role of HSPG sulfation in regulating uterine receptivity by conditionally deleting the N-deacetylase/N-sulfotransferase (NDST) 1 gene (Ndst1) in the mouse uterus using the Pgr-Cre driver, on an Ndst2- and Ndst3-null genetic background. Although development of the female reproductive tract and subsequent ovarian function appear normal in Ndst triple-knockout females, they are infertile due to implantation defects. Embryo attachment appears to occur but the uterine epithelium at the site of implantation persists rather than disintegrates in the mutant. Uterine epithelial cells continued to proliferate past day 4 of pregnancy, accompanied by elevated Fgf2 and Fgf9 expression, whereas uterine stroma failed to undergo decidualization, as evidenced by lack of Bmp2 induction. Despite normal Indian hedgehog expression, transcripts of Ptch1 and Gli1, both components as well as targets of the hedgehog (Hh) pathway, were detected only in the subepithelial stroma, indicating altered Hh signaling in the mutant uterus. Taken together, these data implicate an essential role for HSPGs in modulating signal transduction during mouse implantation.

scholarly journals Synthesizing artificial devices that redirect cellular information at will

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yuchen Liu ◽  
Jianfa Li ◽  
Zhicong Chen ◽  
Weiren Huang ◽  
Zhiming Cai
Keyword(s):  
Cancer Cells ◽  
Signaling Pathway ◽  
Gene Networks ◽  
Target Genes ◽  
Logic Gates ◽  
Feedback Loops ◽  
Oncogenic Signaling ◽  
Multiple Signals ◽  
Translational Level ◽  
At Will

Natural signaling circuits could be rewired to reprogram cells with pre-determined procedures. However, it is difficult to link cellular signals at will. Here, we describe signal-connectors—a series of RNA devices—that connect one signal to another signal at the translational level. We use them to either repress or enhance the translation of target genes in response to signals. Application of these devices allows us to construct various logic gates and to incorporate feedback loops into gene networks. They have also been used to rewire a native signaling pathway and even to create novel pathways. Furthermore, logical AND gates based on these devices and integration of multiple signals have been used successfully for identification and redirection of the state of cancer cells. Eventually, the malignant phenotypes of cancers have been reversed by rewiring the oncogenic signaling from promoting to suppressing tumorigenesis. We provide a novel platform for redirecting cellular information.

Homeotic response elements are tightly linked to tissue-specific elements in a transcriptional enhancer of the teashirt gene

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2799-2812 ◽  
Author(s):  
A. McCormick ◽  
N. Core ◽  
S. Kerridge ◽  
M.P. Scott
Keyword(s):  
Transcriptional Activation ◽  
Target Genes ◽  
Hox Genes ◽  
Zinc Finger Protein ◽  
Cell Types ◽  
Transcriptional Enhancer ◽  
Hox Proteins ◽  
Tissue Specific ◽  
Conserved Sequences

Along the anterior-posterior axis of animal embryos, the choice of cell fates, and the organization of morphogenesis, is regulated by transcription factors encoded by clustered homeotic or ‘Hox’ genes. Hox genes function in both epidermis and internal tissues by regulating the transcription of target genes in a position- and tissue-specific manner. Hox proteins can have distinct targets in different tissues; the mechanisms underlying tissue and homeotic protein specificity are unknown. Light may be shed by studying the organization of target gene enhancers. In flies, one of the target genes is teashirt (tsh), which encodes a zinc finger protein. tsh itself is a homeotic gene that controls trunk versus head development. We identified a tsh gene enhancer that is differentially activated by Hox proteins in epidermis and mesoderm. Sites where Antennapedia (Antp) and Ultrabithorax (Ubx) proteins bind in vitro were mapped within evolutionarily conserved sequences. Although Antp and Ubx bind to identical sites in vitro, Antp activates the tsh enhancer only in epidermis while Ubx activates the tsh enhancer in both epidermis and in somatic mesoderm. We show that the DNA elements driving tissue-specific transcriptional activation by Antp and Ubx are separable. Next to the homeotic protein-binding sites are extensive conserved sequences likely to control tissue activation by different homeodomain proteins. We propose that local interactions between homeotic proteins and other factors effect activation of targets in proper cell types.

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