scholarly journals TCF7L1 and TCF7 differentially regulate specific mouse ES cell genes in response to GSK-3 inhibition

2018 ◽  
Author(s):  
Steven Moreira ◽  
Caleb Seo ◽  
Enio Polena ◽  
Sujeivan Mahendram ◽  
Eloi Mercier ◽  
...  
Keyword(s):  
Target Genes ◽  
Single Copy ◽  
Culture Conditions ◽  
List Type ◽  
Es Cell ◽  
Protein Levels ◽  
Genome Wide ◽  
Pathway Activation ◽  
Standard Serum ◽  
Mouse Es Cell

The genome-wide chromatin occupancy of the TCF/LEF factors and its modulation by Wnt pathway activation remain poorly defined. Here, we describe mouse ES cell (mESC) lines expressing a single copy knock-in of the 3xFLAG epitope at the N-terminus of TCF7L1 and TCF7, the two most-highly expressed TCF/LEF factors in mESCs. TCF7L1 protein levels, detected by immunoblotting with a FLAG antibody, were much higher than TCF7 in mESCs maintained in standard serum- and LIF-supplemented medium, even in the presence of the GSK-3 inhibitor, CHIR99021 (CHIR). We used FLAG antibody-mediated ChIP-seq to determine TCF7 and TCF7L1 chromatin occupancy in mESCs cultured in standard medium with or without CHIR for 14 hours. TCF7 and TCF7L1 displayed very few overlapping ChIP peaks across the genome, with TCF7L1 binding significantly more genes than TCF7 in both culture conditions. Despite a reduction in total TCF7L1 protein after CHIR treatment, the TCF7L1 ChIP peak profiles were not uniformly attenuated. Our data demonstrate that TCF7L1 chromatin occupancy upon short-term CHIR treatment is modulated in a target-specific manner. Our findings also suggest that Wnt target genes in mESCs are not regulated by TCF/LEF switching, and TCF7L1, although often called a constitutive repressor, may serve as a transcriptional activator of certain target genes in CHIR-treated mESCs.HighlightsChIP and cytometry data suggest that TCF7L1 does not directly regulate mESC Nanog expression.TCF7L1 remains associated with β-catenin in the presence of CHIR99021.TCF7 and TCF7L1 display different chromatin occupancies in mESCs.TCF7L1 binding at specific genomic sites is variably altered by CHIR99021.

scholarly journals Genome-Wide, Integrative Analysis Implicates Exosome-Derived MicroRNA Dysregulation in Schizophrenia

2019 ◽  
Vol 45 (6) ◽  
pp. 1257-1266 ◽  
Author(s):  
Yang Du ◽  
Yun Yu ◽  
Yang Hu ◽  
Xiao-Wan Li ◽  
Ze-Xu Wei ◽  
...  
Keyword(s):  
Target Genes ◽  
Sequence Data ◽  
Protein Glycosylation ◽  
Mirna Sequence ◽  
First Episode ◽  
Data Set ◽  
Protein Levels ◽  
Genome Wide ◽  
Exosomal Mirnas ◽  
Mirna Expression Profiling

Abstract Genetic variants conferring risk for schizophrenia (SCZ) have been extensively studied, but the role of posttranscriptional mechanisms in SCZ is not well studied. Here we performed the first genome-wide microRNA (miRNA) expression profiling in serum-derived exosome from 49 first-episode, drug-free SCZ patients and 46 controls and identified miRNAs and co-regulated modules that were perturbed in SCZ. Putative targets of these SCZ-affected miRNAs were enriched strongly for genes that have been implicated in protein glycosylation and were also related to neurotransmitter receptor and dendrite (spine) development. We validated several differentially expressed blood exosomal miRNAs in 100 SCZ patients as compared with 100 controls by quantitative reverse transcription-polymerase chain reaction. The potential regulatory relationships between several SCZ-affected miRNAs and their putative target genes were also validated. These include hsa-miR-206, which is the most upregulated miRNA in the blood exosomes of SCZ patients and that previously reported to regulate brain-derived neurotrophic factor expression, which we showed reduced mRNA and protein levels in the blood of SCZ patients. In addition, we found 11 miRNAs in blood exosomes from the miRNA sequence data that can be used to classify samples from SCZ patients and control subjects with close to 90% accuracy in the training samples, and approximately 75% accuracy in the testing samples. Our findings support a role for exosomal miRNA dysregulation in SCZ pathophysiology and provide a rich data set and framework for future analyses of miRNAs in the disease, and our data also suggest that blood exosomal miRNAs are promising biomarkers for SCZ.

scholarly journals Tracking the embryonic stem cell transition from ground state pluripotency

2016 ◽  
Author(s):  
Tüzer Kalkan ◽  
Nelly Olova ◽  
Mila Roode ◽  
Carla Mulas ◽  
Heather J. Lee ◽  
...  
Keyword(s):  
Ground State ◽  
Es Cells ◽  
Single Cells ◽  
Embryonic Stem ◽  
List Type ◽  
Es Cell ◽  
Genome Wide ◽  
Developmental Progression ◽  
A Genome ◽  
Lineage Priming

SummaryMouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naive pluripotency. Here we examined the initial transition of ES cells. The population behaves asynchronously. We therefore exploited a short-half-life Rex1::GFP reporter to isolate cells either side of exit from naive status. Extinction of ES cell identity in single cells is acute. It occurs only after near-complete elimination of naïve pluripotency factors, but precedes appearance of lineage specification markers. Cells newly departed from the ES cell state exhibit global transcriptome features consistent with features of early post-implantation epiblast and distinct from primed epiblast. They also exhibit a genome-wide increase in DNA methylation, intermediate between early and late epiblast. These findings are consistent with the proposition that naïve cells transition to a discrete formative phase of pluripotency preparatory to lineage priming.HighlightsThe Rex1 destabilized GFP reporter demarcates naive pluripotency.Exit from the naive state is asynchronous in the population.Transition is relatively acute in individual cells and precedes lineage priming.Transcriptome and DNA methylome reflect events in the pre-gastrulation embryo.

scholarly journals RNA polymerase II progression through H3K27me3-enriched gene bodies requires JMJD3 histone demethylase

2013 ◽  
Vol 24 (3) ◽  
pp. 351-360 ◽  
Author(s):  
Conchi Estarás ◽  
Raquel Fueyo ◽  
Naiara Akizu ◽  
Sergi Beltrán ◽  
Marian A. Martínez-Balbás
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Transcriptional Response ◽  
Transforming Growth Factor Β ◽  
Genome Wide ◽  
Pathway Activation

JMJD3 H3K27me3 demethylase plays an important role in the transcriptional response to different signaling pathways; however, the mechanism by which it facilitates transcription has been unclear. Here we show that JMJD3 regulates transcription of transforming growth factor β (TGFβ)–responsive genes by promoting RNA polymerase II (RNAPII) progression along the gene bodies. Using chromatin immunoprecipitation followed by sequencing experiments, we show that, upon TGFβ treatment, JMJD3 and elongating RNAPII colocalize extensively along the intragenic regions of TGFβ target genes. According to these data, genome-wide analysis shows that JMJD3-dependent TGFβ target genes are enriched in H3K27me3 before TGFβ signaling pathway activation. Further molecular analyses demonstrate that JMJD3 demethylates H3K27me3 along the gene bodies, paving the way for the RNAPII progression. Overall these findings uncover the mechanism by which JMJD3 facilitates transcriptional activation.

Induction of melanocyte precursors from neural crest cells surrounding the neural tube-like structures developed in vitro using mouse ES cell culture

2007 ◽  
Vol 27 (1) ◽  
pp. 45-52
Author(s):  
Koh-ichi Atoh ◽  
Manae S. Kurokawa ◽  
Hideshi Yoshikawa ◽  
Chieko Masuda ◽  
Erika Takada ◽  
...  
Keyword(s):  
Cell Culture ◽  
Neural Crest ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Es Cell ◽  
Mouse Es Cell

scholarly journals The mutL Gene as a Genome-Wide Taxonomic Marker for High Resolution Discrimination of Lactiplantibacillus plantarum and Its Closely Related Taxa

2021 ◽  
Vol 9 (8) ◽  
pp. 1570
Author(s):  
Chien-Hsun Huang ◽  
Chih-Chieh Chen ◽  
Yu-Chun Lin ◽  
Chia-Hsuan Chen ◽  
Ai-Yun Lee ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Target Genes ◽  
Marker Genes ◽  
Rrna Gene ◽  
Accurate Identification ◽  
Discrimination Power ◽  
Sequence Identity ◽  
Genome Wide ◽  
A Genome

The current taxonomy of the Lactiplantibacillus plantarum group comprises of 17 closely related species that are indistinguishable from each other by using commonly used 16S rRNA gene sequencing. In this study, a whole-genome-based analysis was carried out for exploring the highly distinguished target genes whose interspecific sequence identity is significantly less than those of 16S rRNA or conventional housekeeping genes. In silico analyses of 774 core genes by the cano-wgMLST_BacCompare analytics platform indicated that csbB, morA, murI, mutL, ntpJ, rutB, trmK, ydaF, and yhhX genes were the most promising candidates. Subsequently, the mutL gene was selected, and the discrimination power was further evaluated using Sanger sequencing. Among the type strains, mutL exhibited a clearly superior sequence identity (61.6–85.6%; average: 66.6%) to the 16S rRNA gene (96.7–100%; average: 98.4%) and the conventional phylogenetic marker genes (e.g., dnaJ, dnaK, pheS, recA, and rpoA), respectively, which could be used to separat tested strains into various species clusters. Consequently, species-specific primers were developed for fast and accurate identification of L. pentosus, L. argentoratensis, L. plantarum, and L. paraplantarum. During this study, one strain (BCRC 06B0048, L. pentosus) exhibited not only relatively low mutL sequence identities (97.0%) but also a low digital DNA–DNA hybridization value (78.1%) with the type strain DSM 20314T, signifying that it exhibits potential for reclassification as a novel subspecies. Our data demonstrate that mutL can be a genome-wide target for identifying and classifying the L. plantarum group species and for differentiating novel taxa from known species.

scholarly journals Genome-wide transcriptome profiling uncovers differential miRNAs and lncRNAs in ovaries of Hu sheep at different developmental stages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samina Shabbir ◽  
Prerona Boruah ◽  
Lingli Xie ◽  
Muhammad Fakhar-e-Alam Kulyar ◽  
Mohsin Nawaz ◽  
...  
Keyword(s):  
Target Genes ◽  
Expression Profiles ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Differentially Expressed ◽  
Ovary Development ◽  
Estrogen Metabolism ◽  
Genome Wide ◽  
Micro Rnas ◽  
Hu Sheep

AbstractOvary development is an important determinant of the procreative capacity of female animals. Here, we performed genome-wide sequencing of long non-coding RNAs (lncRNAs) and mRNAs on ovaries of 1, 3 and 8 months old Hu sheep to assess their expression profiles and roles in ovarian development. We identified 37,309 lncRNAs, 45,404 messenger RNAs (mRNAs) and 330 novel micro RNAs (miRNAs) from the transcriptomic analysis. Six thousand, seven hundred and sixteen (6716) mRNAs and 1972 lncRNAs were significantly and differentially expressed in ovaries of 1 month and 3 months old Hu sheep (H1 vs H3). These mRNAs and target genes of lncRNAs were primarily enriched in the TGF-β and PI3K-Akt signalling pathways which are closely associated with ovarian follicular development and steroid hormone biosynthesis regulation. We identified MSTRG.162061.1, MSTRG.222844.7, MSTRG.335777.1, MSTRG.334059.16, MSTRG.188947.6 and MSTRG.24344.3 as vital genes in ovary development by regulating CTNNB1, CCNA2, CDK2, CDC20, CDK1 and EGFR expressions. A total of 2903 mRNAs and 636 lncRNAs were differentially expressed in 3 and 8 months old ovaries of Hu sheep (H3 vs H8); and were predominantly enriched in PI3K-Akt, progesterone-mediated oocyte maturation, estrogen metabolism, ovulation from the ovarian follicle and oogenesis pathways. These lncRNAs were also found to regulate FGF7, PRLR, PTK2, AMH and INHBA expressions during follicular development. Our result indicates the identified genes participate in the development of the final stages of follicles and ovary development in Hu sheep.

scholarly journals Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tiecheng Wang ◽  
Jiakang Jin ◽  
Chao Qian ◽  
Jianan Lou ◽  
Jinti Lin ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Target Genes ◽  
Target Therapy ◽  
Treatment Strategies ◽  
Signal Transduction Pathway ◽  
Pathway Activation ◽  
Immune System Regulation

AbstractAs the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and β-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.

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