scholarly journals Using 3D epigenomic maps of primary olfactory neuronal cells from living individuals to understand gene regulation

2018 ◽  
Vol 4 (12) ◽  
pp. eaav8550 ◽  
Author(s):  
Suhn K. Rhie ◽  
Shannon Schreiner ◽  
Heather Witt ◽  
Chris Armoskus ◽  
Fides D. Lay ◽  
...  
Keyword(s):  
Cell Model ◽  
Expression Profiles ◽  
Neuronal Cells ◽  
Three Dimensional ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
A Genome ◽  
Wide Scale ◽  
Cell Model System ◽  
Distal Regulatory Elements

As part of PsychENCODE, we developed a three-dimensional (3D) epigenomic map of primary cultured neuronal cells derived from olfactory neuroepithelium (CNON). We mapped topologically associating domains and high-resolution chromatin interactions using Hi-C and identified regulatory elements using chromatin immunoprecipitation and nucleosome positioning assays. Using epigenomic datasets from biopsies of 63 living individuals, we found that epigenetic marks at distal regulatory elements are more variable than marks at proximal regulatory elements. By integrating genotype and metadata, we identified enhancers that have different levels corresponding to differences in genetic variation, gender, smoking, and schizophrenia. Motif searches revealed that many CNON enhancers are bound by neuronal-related transcription factors. Last, we combined 3D epigenomic maps and gene expression profiles to predict enhancer-target gene interactions on a genome-wide scale. This study not only provides a framework for understanding individual epigenetic variation using a primary cell model system but also contributes valuable data resources for epigenomic studies of neuronal epithelium.

scholarly journals Recapitulation-like developmental transitions of chromatin accessibility in vertebrates

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Masahiro Uesaka ◽  
Shigeru Kuratani ◽  
Hiroyuki Takeda ◽  
Naoki Irie
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Evolutionary Developmental Biology ◽  
Chromatin Accessibility ◽  
Putative Gene ◽  
A Genome ◽  
Conserved Gene

AbstractThe relationship between development and evolution has been a central theme in evolutionary developmental biology. Across the vertebrates, the most highly conserved gene expression profiles are found at mid-embryonic, organogenesis stages, whereas those at earlier and later stages are more diverged. This hourglass-like pattern of divergence does not necessarily rule out the possibility that gene expression profiles that are more evolutionarily derived appear at later stages of development; however, no molecular-level evidence of such a phenomenon has been reported. To address this issue, we compared putative gene regulatory elements among different species within a phylum. We made a genome-wide assessment of accessible chromatin regions throughout embryogenesis in three vertebrate species (mouse, chicken, and medaka) and estimated the evolutionary ages of these regions to define their evolutionary origins on the phylogenetic tree. In all the three species, we found that genomic regions tend to become accessible in an order that parallels their phylogenetic history, with evolutionarily newer gene regulations activated at later developmental stages. This tendency was restricted only after the mid-embryonic, phylotypic periods. Our results imply a phylogenetic hierarchy of putative regulatory regions, in which their activation parallels the phylogenetic order of their appearance. One evolutionary mechanism that may explain this phenomenon is that newly introduced regulatory elements are more likely to survive if activated at later stages of embryogenesis. Possible relationships between this phenomenon and the so-called recapitulation are discussed.

scholarly journals Chromatin occupancy analysis reveals genome-wide GATA factor switching during hematopoiesis

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3724-3733 ◽  
Author(s):  
Louis C. Doré ◽  
Timothy M. Chlon ◽  
Christopher D. Brown ◽  
Kevin P. White ◽  
John D. Crispino
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Gata Factor ◽  
Related Factors ◽  
Genome Wide ◽  
A Genome

Abstract There are many examples of transcription factor families whose members control gene expression profiles of diverse cell types. However, the mechanism by which closely related factors occupy distinct regulatory elements and impart lineage specificity is largely undefined. Here we demonstrate on a genome wide scale that the hematopoietic GATA factors GATA-1 and GATA-2 bind overlapping sets of genes, often at distinct sites, as a means to differentially regulate target gene expression and to regulate the balance between proliferation and differentiation. We also reveal that the GATA switch, which entails a chromatin occupancy exchange between GATA2 and GATA1 in the course of differentiation, operates on more than one-third of GATA1 bound genes. The switch is equally likely to lead to transcriptional activation or repression; and in general, GATA1 and GATA2 act oppositely on switch target genes. In addition, we show that genomic regions co-occupied by GATA2 and the ETS factor ETS1 are strongly enriched for regions marked by H3K4me3 and occupied by Pol II. Finally, by comparing GATA1 occupancy in erythroid cells and megakaryocytes, we find that the presence of ETS factor motifs is a major discriminator of megakaryocyte versus red cell specification.

scholarly journals Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1839
Author(s):  
Karolina Seborova ◽  
Radka Vaclavikova ◽  
Lukas Rob ◽  
Pavel Soucek ◽  
Pavel Vodicka
Keyword(s):  
Ovarian Cancer ◽  
Tumor Progression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Distant Metastases ◽  
Regulatory Elements ◽  
Metastatic Spread ◽  
Response To Treatment ◽  
Primary Tumors ◽  
Non Coding Rnas

Ovarian cancer is one of the most common causes of death among gynecological malignancies. Molecular changes occurring in the primary tumor lead to metastatic spread into the peritoneum and the formation of distant metastases. Identification of these changes helps to reveal the nature of metastases development and decipher early biomarkers of prognosis and disease progression. Comparing differences in gene expression profiles between primary tumors and metastases, together with disclosing their epigenetic regulation, provides interesting associations with progression and metastasizing. Regulatory elements from the non-coding RNA families such as microRNAs and long non-coding RNAs seem to participate in these processes and represent potential molecular biomarkers of patient prognosis. Progress in therapy individualization and its proper targeting also rely upon a better understanding of interactions among the above-listed factors. This review aims to summarize currently available findings of microRNAs and long non-coding RNAs linked with tumor progression and metastatic process in ovarian cancer. These biomolecules provide promising tools for monitoring the patient’s response to treatment, and further they serve as potential therapeutic targets of this deadly disease.

scholarly journals Genome-Wide Role of HSF1 in Transcriptional Regulation of Desiccation Tolerance in the Anhydrobiotic Cell Line, Pv11

2021 ◽  
Vol 22 (11) ◽  
pp. 5798
Author(s):  
Shoko Tokumoto ◽  
Yugo Miyata ◽  
Ruslan Deviatiiarov ◽  
Takahiro G. Yamada ◽  
Yusuke Hiki ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Desiccation Tolerance ◽  
Expression Profiles ◽  
Insect Cell Line ◽  
Gene Expression Profiles ◽  
Late Embryogenesis Abundant ◽  
Heat Shock Factor 1 ◽  
Genome Wide ◽  
A Genome

The Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of extreme hypometabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyzing the gene expression profiles of newly established HSF1-knockout and -rescue cell lines, we show that HSF1 has a genome-wide effect on gene regulation in Pv11. The HSF1-knockout cells exhibit a reduced desiccation survival rate, but this is completely restored in HSF1-rescue cells. By comparing mRNA profiles of the two cell lines, we reveal that HSF1 induces anhydrobiosis-related genes, especially genes encoding late embryogenesis abundant proteins and thioredoxins, but represses a group of genes involved in basal cellular processes, thus promoting an extreme hypometabolism state in the cell. In addition, HSF1 binding motifs are enriched in the promoters of anhydrobiosis-related genes and we demonstrate binding of HSF1 to these promoters by ChIP-qPCR. Thus, HSF1 directly regulates the transcription of anhydrobiosis-related genes and consequently plays a pivotal role in the induction of anhydrobiotic ability in Pv11 cells.

scholarly journals Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. e66-e73 ◽  
Author(s):  
Chih-Wen Ni ◽  
Haiwei Qiu ◽  
Amir Rezvan ◽  
Kihwan Kwon ◽  
Douglas Nam ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Profiles ◽  
Disturbed Flow ◽  
A Genome ◽  
Pattern Comparison

Abstract Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genes may provide important insights into understanding vascular biology and atherosclerosis.

scholarly journals Recapitulating tumour microenvironment in chitosan–gelatin three-dimensional scaffolds: an improved in vitro tumour model

2012 ◽  
Vol 9 (77) ◽  
pp. 3288-3302 ◽  
Author(s):  
Neha Arya ◽  
Viren Sardana ◽  
Meera Saxena ◽  
Annapoorni Rangarajan ◽  
Dhirendra S. Katti
Keyword(s):  
Cancer Progression ◽  
Expression Profiles ◽  
Three Dimensional ◽  
Gene Expression Profiles ◽  
Petri Dish ◽  
Tumour Microenvironment ◽  
Two Dimensional ◽  
Tumour Model

Owing to the reduced co-relationship between conventional flat Petri dish culture (two-dimensional) and the tumour microenvironment, there has been a shift towards three-dimensional culture systems that show an improved analogy to the same. In this work, an extracellular matrix (ECM)-mimicking three-dimensional scaffold based on chitosan and gelatin was fabricated and explored for its potential as a tumour model for lung cancer. It was demonstrated that the chitosan–gelatin (CG) scaffolds supported the formation of tumoroids that were similar to tumours grown in vivo for factors involved in tumour-cell–ECM interaction, invasion and metastasis, and response to anti-cancer drugs. On the other hand, the two-dimensional Petri dish surfaces did not demonstrate gene-expression profiles similar to tumours grown in vivo . Further, the three-dimensional CG scaffolds supported the formation of tumoroids, using other types of cancer cells such as breast, cervix and bone, indicating a possible wider potential for in vitro tumoroid generation. Overall, the results demonstrated that CG scaffolds can be an improved in vitro tool to study cancer progression and drug screening for solid tumours.

A genome-wide association study to identify candidate genes for erectile dysfunction

2020 ◽  
Author(s):  
Elham Kazemi ◽  
Javaad Zargooshi ◽  
Marzieh Kaboudi ◽  
Parviz Heidari ◽  
Danial Kahrizi ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Protein Interactions ◽  
Genome Wide Association Study ◽  
Expression Profiles ◽  
Regulatory Elements ◽  
Local Alignment ◽  
Conserved Motifs ◽  
New Genes ◽  
A Genome ◽  
Ucsc Database

Abstract Erectile dysfunction (ED) can be caused by different diseases and controlled by several genetic networks. In this study, to identify the genes related to ED, the expression profiles of normal and ED samples were investigated by the Gene Expression Omnibus (GEO) database. Seventeen genes were identified as associated genes with ED. The protein and nucleic acid sequences of selected genes were retrieved from the UCSC database. Selected genes were diverse according to their physicochemical properties and functions. Category function revealed that selected genes are involved in pathways related to humans some diseases. Furthermore, based on protein interactions, genes associated with the insulin pathway had the greatest interaction with the studied genes. To identify the common cis-regulatory elements, the promoter site of the selected genes was retrieved from the UCSC database. The Gapped Local Alignment of Motifs tool was used for finding common conserved motifs into the promoter site of selected genes. Besides, INSR protein as an insulin receptor precursor showed a high potential site for posttranslation modifications, including phosphorylation and N-glycosylation. Also, in this study, two Guanine-Cytosine (GC)-rich regions were identified as conserved motifs in the upstream of studied genes which can be involved in regulating the expression of genes associated with ED. Also, the conserved binding site of miR-29-3p that is involved in various cancers was observed in the 3′ untranslated region of genes associated with ED. Our study introduced new genes associated with ED, which can be good candidates for further analyzing related to human ED.

scholarly journals Gammaherpesvirus Lytic Gene Expression as Characterized by DNA Array

2002 ◽  
Vol 76 (12) ◽  
pp. 6244-6256 ◽  
Author(s):  
Joo Wook Ahn ◽  
Kenneth L. Powell ◽  
Paul Kellam ◽  
Dagmar G. Alber
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Expression Profiles ◽  
Cdna Array ◽  
Gene Expression Profiles ◽  
Hierarchical Cluster ◽  
Murine Gammaherpesvirus ◽  
Transcription Profiles ◽  
A Genome

ABSTRACT Gammaherpesviruses are associated with a number of diseases including lymphomas and other malignancies. Murine gammaherpesvirus 68 (MHV-68) constitutes the most amenable animal model for this family of pathogens. However experimental characterization of gammaherpesvirus gene expression, at either the protein or RNA level, lags behind that of other, better-studied alpha- and beta-herpesviruses. We have developed a cDNA array to globally characterize MHV-68 gene expression profiles, thus providing an experimental supplement to a genome that is chiefly annotated by homology. Viral genes started to be transcribed as early as 3 h postinfection (p.i.), and this was followed by a rapid escalation of gene expression that could be seen at 5 h p.i. Individual genes showed their own transcription profiles, and most genes were still being expressed at 18 h p.i. Open reading frames (ORFs) M3 (chemokine-binding protein), 52, and M9 (capsid protein) were particularly noticeable due to their very high levels of expression. Hierarchical cluster analysis of transcription profiles revealed four main groups of genes and allowed functional predictions to be made by comparing expression profiles of uncharacterized genes to those of genes of known function. Each gene was also categorized according to kinetic class by blocking de novo protein synthesis and viral DNA replication in vitro. One gene, ORF 73, was found to be expressed with α-kinetics, 30 genes were found to be expressed with β-kinetics, and 42 genes were found to be expressed with γ-kinetics. This fundamental characterization furthers the development of this model and provides an experimental basis for continued investigation of gammaherpesvirus pathology.

scholarly journals Identifying Transcription Regulatory Elements in the Human and Mouse Genomes Using Tissue-specific Gene Expression Profiles

2007 ◽  
Vol 4 (2) ◽  
pp. 1-23
Author(s):  
Amitava Karmaker ◽  
Kihoon Yoon ◽  
Mark Doderer ◽  
Russell Kruzelock ◽  
Stephen Kwek
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Binding Sites ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Tissue Specific Gene ◽  
Human And Mouse

Summary Revealing the complex interaction between trans- and cis-regulatory elements and identifying these potential binding sites are fundamental problems in understanding gene expression. The progresses in ChIP-chip technology facilitate identifying DNA sequences that are recognized by a specific transcription factor. However, protein-DNA binding is a necessary, but not sufficient, condition for transcription regulation. We need to demonstrate that their gene expression levels are correlated to further confirm regulatory relationship. Here, instead of using a linear correlation coefficient, we used a non-linear function that seems to better capture possible regulatory relationships. By analyzing tissue-specific gene expression profiles of human and mouse, we delineate a list of pairs of transcription factor and gene with highly correlated expression levels, which may have regulatory relationships. Using two closely-related species (human and mouse), we perform comparative genome analysis to cross-validate the quality of our prediction. Our findings are confirmed by matching publicly available TFBS databases (like TRANFAC and ConSite) and by reviewing biological literature. For example, according to our analysis, 80% and 85.71% of the targets genes associated with E2F5 and RELB transcription factors have the corresponding known binding sites. We also substantiated our results on some oncogenes with the biomedical literature. Moreover, we performed further analysis on them and found that BCR and DEK may be regulated by some common transcription factors. Similar results for BTG1, FCGR2B and LCK genes were also reported.

Sign in / Sign up

Export Citation Format

Share Document