scholarly journals Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation

2020 ◽  
Vol 52 (2) ◽  
pp. 81-95 ◽  
Author(s):  
Ana M. Mesa ◽  
Jiude Mao ◽  
Manjunatha K. Nanjappa ◽  
Theresa I. Medrano ◽  
Sergei Tevosian ◽  
...  

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that suppresses gene expression. Previously, we developed a conditional null model where EZH2 is knocked out in uterus. Deletion of uterine EZH2 increased proliferation of luminal and glandular epithelial cells. Herein, we used RNA-Seq in wild-type (WT) and EZH2 conditional knockout ( Ezh2cKO) uteri to obtain mechanistic insights into the gene expression changes that underpin the pathogenesis observed in these mice. Ovariectomized adult Ezh2cKO mice were treated with vehicle (V) or 17β-estradiol (E2; 1 ng/g). Uteri were collected at postnatal day (PND) 75 for RNA-Seq or immunostaining for epithelial proliferation. Weighted gene coexpression network analysis was used to link uterine gene expression patterns and epithelial proliferation. In V-treated mice, 88 transcripts were differentially expressed (DEG) in Ezh2cKO mice, and Bmp5, Crabp2, Lgr5, and Sprr2f were upregulated. E2 treatment resulted in 40 DEG with Krt5, Krt15, Olig3, Crabp1, and Serpinb7 upregulated in Ezh2cKO compared with control mice. Transcript analysis relative to proliferation rates revealed two module eigengenes correlated with epithelial proliferation in WT V vs. Ezh2cKO V and WT E2 vs. Ezh2cKO E2 mice, with a positive relationship in the former and inverse in the latter. Notably, the ESR1, Wnt, and Hippo signaling pathways were among those functionally enriched in Ezh2cKO females. Current results reveal unique gene expression patterns in Ezh2cKO uterus and provide insight into how loss of this critical epigenetic regulator assumingly contributes to uterine abnormalities.

2017 ◽  
Author(s):  
Nisar Wani ◽  
Khalid Raza

AbstractGene expression patterns determine the manner whereby organisms regulate various cellular processes and therefore their organ functions.These patterns do not emerge on their own, but as a result of diverse regulatory factors such as, DNA binding proteins known as transcription factors (TF), chromatin structure and various other environmental factors. TFs play a pivotal role in gene regulation by binding to different locations on the genome and influencing the expression of their target genes. Therefore, predicting target genes and their regulation becomes an important task for understanding mechanisms that control cellular processes governing both healthy and diseased cells.In this paper, we propose an integrated inference pipeline for predicting target genes and their regulatory effects for a specific TF using next-generation data analysis tools.


2020 ◽  
Author(s):  
Timothy J. Durham ◽  
Riza M. Daza ◽  
Louis Gevirtzman ◽  
Darren A. Cusanovich ◽  
William Stafford Noble ◽  
...  

AbstractRecently developed single cell technologies allow researchers to characterize cell states at ever greater resolution and scale. C. elegans is a particularly tractable system for studying development, and recent single cell RNA-seq studies characterized the gene expression patterns for nearly every cell type in the embryo and at the second larval stage (L2). Gene expression patterns are useful for learning about gene function and give insight into the biochemical state of different cell types; however, in order to understand these cell types, we must also determine how these gene expression levels are regulated. We present the first single cell ATAC-seq study in C. elegans. We collected data in L2 larvae to match the available single cell RNA-seq data set, and we identify tissue-specific chromatin accessibility patterns that align well with existing data, including the L2 single cell RNA-seq results. Using a novel implementation of the latent Dirichlet allocation algorithm, we leverage the single-cell resolution of the sci-ATAC-seq data to identify accessible loci at the level of individual cell types, providing new maps of putative cell type-specific gene regulatory sites, with promise for better understanding of cellular differentiation and gene regulation in the worm.


Gene ◽  
2021 ◽  
pp. 146090
Author(s):  
Karolina Wiśniewska ◽  
Lidia Gaffke ◽  
Karolina Krzelowska ◽  
Grzegorz Węgrzyn ◽  
Karolina Pierzynowska

2020 ◽  
Author(s):  
Kyungmin Ahn ◽  
Hironobu Fujiwara

Statement of withdrawalThe authors have withdrawn version 1 of this manuscript because a draft manuscript, which was still in the early stages of preparation and required major revisions including the replacement of the source RNA-seq datasets, was erroneously submitted. The authors do not wish this version to be cited as reference for this study. We will post a revised manuscript in the future. If you have any questions, please contact the corresponding author.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ashok Kumar Sharma ◽  
Barbora Pafčo ◽  
Klára Vlčková ◽  
Barbora Červená ◽  
Jakub Kreisinger ◽  
...  

2014 ◽  
Vol 221 (3) ◽  
pp. 429-440 ◽  
Author(s):  
Wenxia He ◽  
Xiangyan Dai ◽  
Xiaowen Chen ◽  
Jiangyan He ◽  
Zhan Yin

Sexual maturation and somatic growth cessation are associated with adolescent development, which is precisely controlled by interconnected neuroendocrine regulatory pathways in the endogenous endocrine system. The pituitary gland is one of the key regulators of the endocrine system. By analyzing the RNA sequencing (RNA-seq) transcriptome before and after sexual maturation, in this study, we characterized the global gene expression patterns in zebrafish pituitaries at 45 and 90 days post-fertilization (dpf). A total of 15 043 annotated genes were expressed in the pituitary tissue, 3072 of which were differentially expressed with a greater than or equal to twofold change between pituitaries at 45 and 90 dpf. In the pituitary transcriptome, the most abundant transcript was gh. The expression levels of gh remained high even after sexual maturation at 90 dpf. Among the eight major pituitary hormone genes, lhb was the only gene that exhibited a significant change in its expression levels between 45 and 90 dpf. Significant changes in the pituitary transcripts included genes involved in the regulation of immune responses, bone metabolism, and hormone secretion processes during the juvenile–sexual maturity transition. Real-time quantitative PCR analysis was carried out to verify the RNA-seq transcriptome results and demonstrated that the expression patterns of the eight major pituitary hormone genes did not exhibit a significant gender difference at 90 dpf. For the first time, we report the quantitative global gene expression patterns at the juvenile and sexual maturity stages. These expression patterns may account for the dynamic neuroendocrine regulation observed in body metabolism.


2021 ◽  
Author(s):  
Peter G Vaughan-Shaw ◽  
Graeme Grimes ◽  
James P Blackmur ◽  
Maria Timofeeva ◽  
Marion Walker ◽  
...  

Background Risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in-vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. Methods Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). Results 629 genes were associated with 25-OHD level (P<0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P<1.0E-07; downregulated gene-set P<2.6E-05) and corresponding GO terms (P=2.90E-02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P<0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI:0.66-1.00]), and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI:0.77-0.89]; PPP1CC AUC=0.91 [95%CI:0.86-0.95]). Conclusions Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumor transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response.


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