scholarly journals Integration of ATAC-seq and RNA-seq Unravels Chromatin Accessibility during Sex Reversal in Orange-Spotted Grouper (Epinephelus coioides)

2020 ◽  
Vol 21 (8) ◽  
pp. 2800 ◽  
Author(s):  
Xi Wu ◽  
Yang Yang ◽  
Chaoyue Zhong ◽  
Yin Guo ◽  
Tengyu Wei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Sex Reversal ◽  
Open Chromatin ◽  
Specific Marker ◽  
Epinephelus Coioides ◽  
Rna Seq ◽  
Accessible Chromatin

Chromatin structure plays a pivotal role in maintaining the precise regulation of gene expression. Accessible chromatin regions act as the binding sites of transcription factors (TFs) and cis-elements. Therefore, information from these open regions will enhance our understanding of the relationship between TF binding, chromatin status and the regulation of gene expression. We employed an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA-seq analyses in the gonads of protogynous hermaphroditic orange-spotted groupers during sex reversal to profile open chromatin regions and TF binding sites. We focused on several crucial TFs, including ZNF263, SPIB, and KLF9, and analyzed the networks of TF-target genes. We identified numerous transcripts exhibiting sex-preferred expression among their target genes, along with their associated open chromatin regions. We then investigated the expression patterns of sex-related genes as well as the mRNA localization of certain genes during sex reversal. We found a set of sex-related genes that—upon further study—might be identified as the sex-specific or cell-specific marker genes that trigger sex reversal. Moreover, we discovered the core genes (gnas, ccnb2, and cyp21a) of several pathways related to sex reversal that provide the guideposts for future study.

scholarly journals Chromatin Loop Anchors Are Core Structural Components of the Gene Expression Machinery in Maize

2020 ◽  
Author(s):  
Stephane Deschamps ◽  
John A Crow ◽  
Nadia Chaidir ◽  
Brooke Peterson-Burch ◽  
Sunil Kumar ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Transcriptional Activity ◽  
Spatial Organization ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Regulatory Elements ◽  
Open Chromatin ◽  
Chromatin Loop ◽  
Chromatin Loops

Abstract Background Three-dimensional chromatin loop structures connect regulatory elements to their target genes in regions known as anchors. In complex plant genomes, such as maize, it has been proposed that loops span heterochromatic regions marked by higher repeat content, but little is known on their spatial organization and genome-wide occurrence in relation to transcriptional activity. Results Here, ultra-deep Hi-C sequencing of maize B73 leaf tissue was combined with gene expression and open chromatin sequencing for chromatin loop discovery and correlation with transcriptional activity. Chromatin loops, made of two “anchors” flanking a loop “interior”, overlap with up to 90% of high-resolution interaction domains from a previous public maize interactome dataset. A majority of all anchors are shared between multiple loops, suggesting a highly dynamic environment, with a conserved set of anchors involved in multiple interaction networks. Chromatin loop interiors are marked by higher repeat contents than the anchors flanking them. A small fraction of high-resolution interaction anchors, fully embedded in larger chromatin loops, co-locate with active genes and putative protein-binding sites. Combinatorial analysis indicate that all anchors studied here co-locate with at least 81.5% of expressed genes and 74% of open chromatin regions. Up to 63% of all unique variants derived from a prior public maize eQTL datasets overlap with Hi-C loop anchors. Anchor annotation suggests that <7% of all loops detected from one Hi-C library are potentially devoid of any genes or regulatory elements. The overall conservation and organization of chromatin loop anchors in the maize genome suggest a loop modeling system hypothesized to resemble phase separation of repeat-rich regions. Conclusions A majority of expressed genes and open chromatin regions co-locate with a conserved set of chromatin loop anchors. The results presented here will be a useful reference to further investigate the function of chromatin loop anchors and of the formation of interaction regions in the regulation of gene expression in maize.

scholarly journals Cell cycle progression inCaulobacterrequires a nucleoid-associated protein with high AT sequence recognition

2016 ◽  
Vol 113 (40) ◽  
pp. E5952-E5961 ◽  
Author(s):  
Dante P. Ricci ◽  
Michael D. Melfi ◽  
Keren Lasker ◽  
David L. Dill ◽  
Harley H. McAdams ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Binding Sites ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Caulobacter Crescentus ◽  
Regulation Of Gene Expression ◽  
Cycle Progression ◽  
Swarmer Cell ◽  
Sequence Recognition

Faithful cell cycle progression in the dimorphic bacteriumCaulobacter crescentusrequires spatiotemporal regulation of gene expression and cell pole differentiation. We discovered an essential DNA-associated protein, GapR, that is required forCaulobactergrowth and asymmetric division. GapR interacts with adenine and thymine (AT)-rich chromosomal loci, associates with the promoter regions of cell cycle-regulated genes, and shares hundreds of recognition sites in common with known master regulators of cell cycle-dependent gene expression. GapR target loci are especially enriched in binding sites for the transcription factors GcrA and CtrA and overlap with nearly all of the binding sites for MucR1, a regulator that controls the establishment of swarmer cell fate. Despite constitutive synthesis, GapR accumulates preferentially in the swarmer compartment of the predivisional cell. Homologs of GapR, which are ubiquitous among the α-proteobacteria and are encoded on multiple bacteriophage genomes, also accumulate in the predivisional cell swarmer compartment when expressed inCaulobacter. TheEscherichia colinucleoid-associated protein H-NS, like GapR, selectively associates with AT-rich DNA, yet it does not localize preferentially to the swarmer compartment when expressed exogenously inCaulobacter, suggesting that recognition of AT-rich DNA is not sufficient for the asymmetric accumulation of GapR. Further, GapR does not silence the expression of H-NS target genes when expressed inE. coli, suggesting that GapR and H-NS have distinct functions. We propose thatCaulobacterhas co-opted a nucleoid-associated protein with high AT recognition to serve as a mediator of cell cycle progression.

scholarly journals 32 Functional annotation of livestock genomes: chromatin structure and regulation of gene expression

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 15-16
Author(s):  
Sylvain Foissac ◽  
Sarah Djebali ◽  
Kylie Munyard ◽  
Nathalie Vialaneix ◽  
Andrea Rau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Functional Annotation ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Rna Seq ◽  
Chromosome Conformation ◽  
Accessible Chromatin ◽  
Animal Genomes

Abstract Improving the functional annotation of animal genomes is a key challenge in bridging the gap between genotype and phenotype, thus enabling predictive biology. Regarding livestock production, major outcomes are expected from a better understanding of the genetic architecture underlying quantitative traits. As part of the Functional Annotation of ANimal Genomes action (FAANG: www.faang.org), the FR-AgENCODE project generated omics data to improve the reference annotation of the cattle, pig, goat and chicken genome. High-throughput molecular assays have been performed on tissues/cells relevant to immune and metabolic traits. From two males and two females per species (pig, cattle, goat, chicken), strand-oriented RNA-seq gene expression and ATAC-seq chromatin accessibility assays were performed on liver and two PBMC-sorted T-cell types (CD4+ and CD8+). Chromosome Conformation Capture (in situ Hi-C) was also carried out on liver samples. About 4,000 samples have been collected at the INRA biorepository and registered at the EBI BioSamples registry. More than 80% of the planned experiments could be completed, generating ~11.5 billions of sequencing reads over the 3 assays. While most (50–80%) RNA-seq reads mapped to annotated exons, thousands of novel transcripts were found, with ~60K mRNAs and ~22K lncRNAs in cattle. Differentially expressed genes between cell types were enriched for immunity- or metabolism-related terms, and differentially accessible chromatin regions were identified as potential regulatory sites. Interestingly, correlations between gene expression and promoter accessibility across samples were skewed towards both positive and negative values, suggesting distinct regulatory mechanisms of gene expression. These patterns have been further investigated using human data from the Epigenome Roadmap Mapping Consortium. Altogether, this study illustrates the interest of a coordinated effort to tackle the genome-to-phenome challenge and provides a useful resource to the community. Availability: www.fragencode.org.

scholarly journals RNA-Seq reveals novel genes and pathways associated with hypoxia duration and tolerance in tomato root

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vajiheh Safavi-Rizi ◽  
Marco Herde ◽  
Christine Stöhr
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Fine Tuning ◽  
Hypoxia Tolerance ◽  
Hypoxic Stress ◽  
Rna Seq ◽  
Aerenchyma Formation ◽  
Tomato Root

AbstractDue to climate change, economically important crop plants will encounter flooding periods causing hypoxic stress more frequently. This may lead to reduced yields and endanger food security. As roots are the first organ to be affected by hypoxia, the ability to sense and respond to hypoxic stress is crucial. At the molecular level, therefore, fine-tuning the regulation of gene expression in the root is essential for hypoxia tolerance. Using an RNA-Seq approach, we investigated transcriptome modulation in tomato roots of the cultivar ‘Moneymaker’, in response to short- (6 h) and long-term (48 h) hypoxia. Hypoxia duration appeared to have a significant impact on gene expression such that the roots of five weeks old tomato plants showed a distinct time-dependent transcriptome response. We observed expression changes in 267 and 1421 genes under short- and long-term hypoxia, respectively. Among these, 243 genes experienced changed expression at both time points. We identified tomato genes with a potential role in aerenchyma formation which facilitates oxygen transport and may act as an escape mechanism enabling hypoxia tolerance. Moreover, we identified differentially regulated genes related to carbon and amino acid metabolism and redox homeostasis. Of particular interest were the differentially regulated transcription factors, which act as master regulators of downstream target genes involved in responses to short and/or long-term hypoxia. Our data suggest a temporal metabolic and anatomic adjustment to hypoxia in tomato root which requires further investigation. We propose that the regulated genes identified in this study are good candidates for further studies regarding hypoxia tolerance in tomato or other crops.

scholarly journals Regulation of gene expression by the APP family in the adult cerebral cortex

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Hye Ji Cha ◽  
Jie Shen ◽  
Jongkyun Kang
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Mrna Levels ◽  
Rna Seq ◽  
Cellular Functions ◽  
Organization Learning ◽  
Transcriptional Changes

AbstractAmyloid precursor protein (APP) is associated with both familial and sporadic forms of Alzheimer’s disease. APP has two homologs, amyloid precursor-like protein 1 and 2 (APLP1 and APLP2), and they have functional redundancy. APP intracellular c-terminal domain (AICD), produced by sequential α- or β- and γ-secretase cleavages, is thought to control gene expression, similarly as the ICD of Notch. To investigate the role of APP family in transcriptional regulation, we examined gene expression changes in the cerebral cortex of APP/APLP1/APLP2 conditional triple knockout (cTKO) mice, in which APP family members are selectively inactivated in excitatory neurons of the postnatal forebrain. Of the 12 previously reported AICD target genes, only Nep and Npas4 mRNA levels were significantly reduced in the cerebral cortex of cTKO mice, compared to littermate controls. We further examined global transcriptional changes by RNA-seq and identified 189 and 274 differentially expressed genes in the neocortex and hippocampus, respectively, of cTKO mice relative to controls. Gene Ontology analysis indicated that these genes are involved in a variety of cellular functions, including extracellular organization, learning and memory, and ion channels. Thus, inactivation of APP family alters transcriptional profiles of the cerebral cortex and affects wide-ranging molecular pathways.

scholarly journals Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Lago ◽  
Matteo Nadai ◽  
Filippo M. Cernilogar ◽  
Maryam Kazerani ◽  
Helena Domíniguez Moreno ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Gene ◽  
Open Chromatin ◽  
Rna Seq ◽  
Transcript Levels ◽  
Promoter Sequences ◽  
G Quadruplex ◽  
Cell Type Specific ◽  
Folding State

AbstractCell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus, G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s to strongly emerge as new epigenetic regulators of the transcription machinery.

scholarly journals EPEN-30. C11ORF95-RELA FUSION PROTEIN ENGAGES NOVEL GENOMIC LOCI TO DRIVE MURINE EPENDYMOMA GROWTH

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii314-iii314
Author(s):  
Amir Arabzade ◽  
Yanhua Zhao ◽  
Srinidhi Varadharajan ◽  
Hsiao-Chi Chen ◽  
Austin Stuckert ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Molecular Targets ◽  
Lead Target ◽  
Open Chromatin ◽  
Rna Seq ◽  
In Utero Electroporation ◽  
Pathway Activation ◽  
Mouse Cells ◽  
Shed Light

Abstract RATIONALE Over 70% of supratentorial (ST) ependymoma are characterized by an oncogenic fusion between C11ORF95 and RELA. C11ORF95-RELA fusion is frequently the sole genetic driver detected in ST ependymoma, thus ranking this genomic event as a lead target for therapeutic investigation. RELA is a transcription factor (TF) central to mediating NF-kB pathway activation in processes such as inflammation, cellular metabolism, and chemotaxis. HYPOTHESIS: We posited that C11ORF95-RELA acts as an oncogenic TF that aberrantly shapes the tumor epigenome to drive aberrant transcription. Approach: To this end we developed an in utero electroporation (IUE) mouse model of ependymoma to express C11ORF95-RELA during embryonic development. Our IUE approach allowed us to develop C11ORF95-RELA driven tumor models and cell lines. We comprehensively characterized the epigenome and transcriptome of C11ORF95-RELA fusion driven mouse cells by H3K27ac ChIP-seq, ATAC-seq, and RNA-seq. RESULTS This data revealed that: 1) C11ORF95-RELA directly engages ‘open’ chromatin and is enriched at regions with known RELA TF binding sites as well as novel genomic loci/motifs, 2) C11ORF95-RELA preferentially binds to both H3K27ac (active) enhancers and promoters, and 3) Bound C11ORF95-RELA promoter loci are associated with increased transcription of genes shared with human ependymoma. CONCLUSION Our findings shed light on the transcriptional mechanisms of C11ORF95-RELA, and reveal downstream targets that may represent cancer dependency genes and molecular targets.

scholarly journals Complex fibroblast response to glucocorticoids may underlie variability of clinical efficacy in the vocal folds

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryosuke Nakamura ◽  
Shigeyuki Mukudai ◽  
Renjie Bing ◽  
Michael J. Garabedian ◽  
Ryan C. Branski
Keyword(s):  
Gene Expression ◽  
Transforming Growth Factor ◽  
Regulation Of Gene Expression ◽  
Vocal Folds ◽  
Global Changes ◽  
Rna Seq ◽  
Fibrotic Response ◽  
Group A ◽  
Tgf Β1 ◽  
Nuclear Receptor Subfamily

AbstractSimilar to the hypertrophic scar and keloids, the efficacy of glucorticoids (GC) for vocal fold injury is highly variable. We previously reported dexamethasone enhanced the pro-fibrotic effects of transforming growth factor (TGF)-β as a potential mechanism for inconsistent clinical outcomes. In the current study, we sought to determine the mechanism(s) whereby GCs influence the fibrotic response and mechanisms underlying these effects with an emphasis on TGF-β and nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling. Human VF fibroblasts (HVOX) were treated with three commonly-employed GCs+ /-TGF-β1. Phosphorylation of the glucocorticoid receptor (GR:NR3C1) and activation of NR4A1 was analyzed by western blotting. Genes involved in the fibrotic response, including ACTA2, TGFBR1, and TGFBR2 were analyzed by qPCR. RNA-seq was performed to identify global changes in gene expression induced by dexamethasone. GCs enhanced phosphorylation of GR at Ser211 and TGF-β-induced ACTA2 expression. Dexamethasone upregulated TGFBR1, and TGFBR2 in the presence of TGF-β1 and increased active NR4A1. RNA-seq results confirmed numerous pathways, including TGF-β signaling, affected by dexamethasone. Synergistic pro-fibrotic effects of TGF-β were observed across GCs and appeared to be mediated, at least partially, via upregulation of TGF-β receptors. Dexamethasone exhibited diverse regulation of gene expression including NR4A1 upregulation consistent with the anti-fibrotic potential of GCs.

The search of CAR, AhR, ESRs binding sites in promoters of intronic and intergenic microRNAs

2018 ◽  
Vol 16 (01) ◽  
pp. 1750029 ◽  
Author(s):  
Vladimir Y. Ovchinnikov ◽  
Denis V. Antonets ◽  
Lyudmila F. Gulyaeva
Keyword(s):  
Transcriptional Activation ◽  
Binding Sites ◽  
In Silico ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Regulation Of Gene Expression ◽  
Experimental Studies ◽  
Transcriptional Level ◽  
Aryl Hydrocarbon ◽  
Exogenous Compounds

MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the post-transcriptional level. Many exogenous compounds or xenobiotics may affect microRNA expression. It is a well-established fact that xenobiotics with planar structure like TCDD, benzo(a)pyrene (BP) can bind aryl hydrocarbon receptor (AhR) followed by its nuclear translocation and transcriptional activation of target genes. Another chemically diverse group of xenobiotics including phenobarbital, DDT, can activate the nuclear receptor CAR and in some cases estrogen receptors ESR1 and ESR2. We hypothesized that such chemicals can affect miRNA expression through the activation of AHR, CAR, and ESRs. To prove this statement, we used in silico methods to find DRE, PBEM, ERE potential binding sites for these receptors, respectively. We have predicted AhR, CAR, and ESRs binding sites in 224 rat, 201 mouse, and 232 human promoters of miRNA-coding genes. In addition, we have identified a number of miRNAs with predicted AhR, CAR, and ESRs binding sites that are known as oncogenes and as tumor suppressors. Our results, obtained in silico, open a new strategy for ongoing experimental studies and will contribute to further investigation of epigenetic mechanisms of carcinogenesis.

A TRIPARTITE CLUSTERING ANALYSIS ON MICRORNA, GENE AND DISEASE MODEL

2012 ◽  
Vol 10 (01) ◽  
pp. 1240007 ◽  
Author(s):  
CHENGCHENG SHEN ◽  
YING LIU
Keyword(s):  
Gene Expression ◽  
Clustering Algorithm ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Disease Model ◽  
Relational Information ◽  
Microrna Gene ◽  
Research Findings ◽  
Family Based

Alteration of gene expression in response to regulatory molecules or mutations could lead to different diseases. MicroRNAs (miRNAs) have been discovered to be involved in regulation of gene expression and a wide variety of diseases. In a tripartite biological network of human miRNAs, their predicted target genes and the diseases caused by altered expressions of these genes, valuable knowledge about the pathogenicity of miRNAs, involved genes and related disease classes can be revealed by co-clustering miRNAs, target genes and diseases simultaneously. Tripartite co-clustering can lead to more informative results than traditional co-clustering with only two kinds of members and pass the hidden relational information along the relation chain by considering multi-type members. Here we report a spectral co-clustering algorithm for k-partite graph to find clusters with heterogeneous members. We use the method to explore the potential relationships among miRNAs, genes and diseases. The clusters obtained from the algorithm have significantly higher density than randomly selected clusters, which means members in the same cluster are more likely to have common connections. Results also show that miRNAs in the same family based on the hairpin sequences tend to belong to the same cluster. We also validate the clustering results by checking the correlation of enriched gene functions and disease classes in the same cluster. Finally, widely studied miR-17-92 and its paralogs are analyzed as a case study to reveal that genes and diseases co-clustered with the miRNAs are in accordance with current research findings.

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