scholarly journals Transposable element exaptation is the primary source of novelty in the primate gene regulatory landscape

2016 ◽  
Author(s):  
Marco Trizzino ◽  
YoSon Park ◽  
Marcia Holsbach-Beltrame ◽  
Katherine Aracena ◽  
Katelyn Mika ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Phenotypic Diversity ◽  
Regulatory Element ◽  
Critical Role ◽  
Primary Source ◽  
Primate Species ◽  
Rna Seq ◽  
Cell Type Specificity ◽  
Regulatory Landscape

AbstractGene regulation plays a critical role in the evolution of phenotypic diversity. We investigated the evolution of liver promoters and enhancers in six primate species. We performed ChlP-seq for two histone modifications and RNA-seq to profile cis-regulatory element (CRE) activity and gene expression. The primate regulatory landscape is largely conserved across the lineage. Conserved CRE function is associated with sequence conservation, proximity to coding genes, cell type specificity of CRE function, and transcription factor binding. Newly evolved CREs are enriched in immune response and neurodevelopmental functions, while conserved CREs bind master regulators. Transposable elements (TEs) are the primary source of novelty in primate gene regulation. Newly evolved CREs are enriched in young TEs that affect gene expression. However, only 17% of conserved CREs overlap a TE, suggesting that target gene expression is under strong selection. Finally, we identified specific genomic features driving the functional recruitment of newly inserted TEs.

The characteristics of mesenteric adipose tissue attached to different intestinal segments and their roles in immune regulation

2022 ◽  
Author(s):  
Haowei Zhang ◽  
Yujin Ding ◽  
Qin Zeng ◽  
Dandan Wang ◽  
Ganglei Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Immune Regulation ◽  
Expression Profiles ◽  
Critical Role ◽  
Gene Expression Profiles ◽  
Rna Seq ◽  
Mesenteric Adipose Tissue ◽  
Cell Components ◽  
Subsequent Effect

Background: Mesenteric adipose tissue (MAT) plays a critical role in the intestinal physiological ecosystems. Small and large intestines have evidently intrinsic and distinct characteristics. However, whether there exist any mesenteric differences adjacent to the small and large intestines (SMAT and LMAT) has not been properly characterized. We studied the important facets of these differences, such as morphology, gene expression, cell components and immune regulation of MATs, to characterize the mesenteric differences. Methods: The SMAT and LMAT of mice were utilized for comparison of tissue morphology. Paired mesenteric samples were analyzed by RNA-seq to clarify gene expression profiles. MAT partial excision models were constructed to illustrate the immune regulation roles of MATs, and 16S-seq was applied to detect the subsequent effect on microbiota. Results: Our data show that different segments of mesenteries have different morphological structures. SMAT not only has smaller adipocytes but also contains more fat-associated lymphoid clusters than LMAT. The gene expression profile is also discrepant between these two MATs in mice. B-cell markers were abundantly expressed in SMAT, while development-related genes were highly expressed in LMAT. Adipose-derived stem cells of LMAT exhibited higher adipogenic potential and lower proliferation rates than those of SMAT. In addition, SMAT and LMAT play different roles in immune regulation and subsequently affect microbiota components. Finally, our data clarified the described differences between SMAT and LMAT in humans. Conclusions: There were significant differences in cell morphology, gene expression profiles, cell components, biological characteristics, and immune and microbiota regulation roles between regional MATs.

scholarly journals Microbial control of host gene regulation and the evolution of host–microbiome interactions in primates

2020 ◽  
Vol 375 (1808) ◽  
pp. 20190598 ◽  
Author(s):  
Laura Grieneisen ◽  
Amanda L. Muehlbauer ◽  
Ran Blekhman
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Host Species ◽  
Evolutionary Dynamics ◽  
Microbial Control ◽  
Host Gene ◽  
Primate Species ◽  
Microbiome Composition ◽  
Wide Range ◽  
Species Specific

Recent comparative studies have found evidence consistent with the action of natural selection on gene regulation across primate species. Other recent work has shown that the microbiome can regulate host gene expression in a wide range of relevant tissues, leading to downstream effects on immunity, metabolism and other biological systems in the host. In primates, even closely related host species can have large differences in microbiome composition. One potential consequence of these differences is that host species-specific microbial traits could lead to differences in gene expression that influence primate physiology and adaptation to local environments. Here, we will discuss and integrate recent findings from primate comparative genomics and microbiome research, and explore the notion that the microbiome can influence host evolutionary dynamics by affecting gene regulation across primate host species. This article is part of the theme issue ‘The role of the microbiome in host evolution’.

scholarly journals RBPMetaDB: A comprehensive annotation of mouse RNA-Seq datasets with perturbations of RNA-binding proteins

2018 ◽  
Author(s):  
Jin Li ◽  
Su-Ping Deng ◽  
Jacob Vieira ◽  
James Thomas ◽  
Valerio Costa ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Dna Binding ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Experimental Studies ◽  
Easy Access ◽  
Rna Seq ◽  
Mrna Stabilization

AbstractRNA-binding proteins may play a critical role in gene regulation in various diseases or biological processes by controlling post-transcriptional events such as polyadenylation, splicing, and mRNA stabilization via binding activities to RNA molecules. Due to the importance of RNA-binding proteins in gene regulation, a great number of studies have been conducted, resulting in a large amount of RNA-Seq datasets. However, these datasets usually do not have structured organization of metadata, which limits their potentially wide use. To bridge this gap, the metadata of a comprehensive set of publicly available mouse RNA-Seq datasets with perturbed RNA-binding proteins were collected and integrated into a database called RBPMetaDB. This database contains 278 mouse RNA-Seq datasets for a comprehensive list of 163 RNA-binding proteins. These RNA-binding proteins account for only ∼10% of all known RNA-binding proteins annotated in Gene Ontology, indicating that most are still unexplored using high-throughput sequencing. This negative information provides a great pool of candidate RNA-binding proteins for biologists to conduct future experimental studies. In addition, we found that DNA-binding activities are significantly enriched among RNA-binding proteins in RBPMetaDB, suggesting that prior studies of these DNA- and RNA-binding factors focus more on DNA-binding activities instead of RNA-binding activities. This result reveals the opportunity to efficiently reuse these data for investigation of the roles of their RNA-binding activities. A web application has also been implemented to enable easy access and wide use of RBPMetaDB. It is expected that RBPMetaDB will be a great resource for improving understanding of the biological roles of RNA-binding proteins.Database URL: http://rbpmetadb.yubiolab.org

scholarly journals Analysis of thein plantatranscriptome expressed by the corn pathogenPantoea stewartiisubsp.stewartiivia RNA-Seq

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3237 ◽  
Author(s):  
Holly Packard ◽  
Alison Kernell Burke ◽  
Roderick V. Jensen ◽  
Ann M. Stevens
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Critical Role ◽  
Wilt Disease ◽  
Sample Type ◽  
Dependent Manner ◽  
Rna Seq ◽  
In Planta ◽  
Data Set

Pantoea stewartiisubsp.stewartiiis a bacterial phytopathogen that causes Stewart’s wilt disease in corn. It uses quorum sensing to regulate expression of some genes involved in virulence in a cell density-dependent manner as the bacterial population grows from small numbers at the initial infection site in the leaf apoplast to high cell numbers in the xylem where it forms a biofilm. There are also other genes important for pathogenesis not under quorum-sensing control such as a Type III secretion system. The purpose of this study was to compare gene expression during anin plantainfection versus either a pre-inoculumin vitroliquid culture or anin vitroagar plate culture to identify genes specifically expressedin plantathat may also be important for colonization and/or virulence. RNA was purified from each sample type to determine the transcriptome via RNA-Seq using Illumina sequencing of cDNA. Fold gene expression changes in thein plantadata set in comparison to the twoin vitrogrown samples were determined and a list of the most differentially expressed genes was generated to elucidate genes important for plant association. Quantitative reverse transcription PCR (qRT-PCR) was used to validate expression patterns for a select subset of genes. Analysis of the transcriptome data via gene ontology revealed that bacterial transporters and systems important for oxidation reduction processes appear to play a critical role forP. stewartiias it colonizes and causes wilt disease in corn plants.

scholarly journals Potential Autoregulation of Transcription Factor PU.1 by an Upstream Regulatory Element

2005 ◽  
Vol 25 (7) ◽  
pp. 2832-2845 ◽  
Author(s):  
Yutaka Okuno ◽  
Gang Huang ◽  
Frank Rosenbauer ◽  
Erica K. Evans ◽  
Hanna S. Radomska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Reporter Gene ◽  
Regulatory Element ◽  
Mammalian Species ◽  
Critical Role ◽  
Homologous Region ◽  
Specific Expression ◽  
Upstream Regulatory Element

ABSTRACT Regulation of the hematopoietic transcription factor PU.1 (Spi-1) plays a critical role in the development of white cells, and abnormal expression of PU.1 can lead to leukemia. We previously reported that the PU.1 promoter cannot induce expression of a reporter gene in vivo, and cell-type-specific expression of PU.1 in stable lines was conferred by a 3.4-kb DNA fragment including a DNase I hypersensitive site located 14 kb upstream of the transcription start site. Here we demonstrate that this kb −14 site confers lineage-specific reporter gene expression in vivo. This kb −14 upstream regulatory element contains two 300-bp regions which are highly conserved in five mammalian species. In Friend virus-induced erythroleukemia, the spleen focus-forming virus integrates into the PU.1 locus between these two conserved regions. DNA binding experiments demonstrated that PU.1 itself and Elf-1 bind to a highly conserved site within the proximal homologous region in vivo. A mutation of this site abolishing binding of PU.1 and Elf-1 led to a marked decrease in the ability of this upstream element to direct activity of reporter gene in myelomonocytic cell lines. These data suggest that a potential positive autoregulatory loop mediated through an upstream regulatory element is essential for proper PU.1 gene expression.

scholarly journals Induction of Human Liver X Receptor α Gene Expression Via an Autoregulatory Loop Mechanism

2002 ◽  
Vol 16 (3) ◽  
pp. 506-514 ◽  
Author(s):  
Yu Li ◽  
Charles Bolten ◽  
B. Ganesh Bhat ◽  
Jessica Woodring-Dietz ◽  
Suzhen Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Regulatory Element ◽  
Critical Role ◽  
Cell Types ◽  
Plasma Lipoproteins ◽  
Type I ◽  
Type Ii ◽  
Downstream Target ◽  
X Receptors

Abstract The liver X receptors (LXRs), members of the nuclear receptor superfamily, play an important role in controlling lipid homeostasis by activating several genes involved in reverse cholesterol transport. These include members of the ATP binding cassette (ABC) superfamily of transporter proteins ABCA1 and ABCG1, surface constituents of plasma lipoproteins like apolipoprotein E, and cholesterol ester transport protein. They also play an important role in fatty acid metabolism by activating the sterol regulatory element-binding protein 1c gene. Here, we identify human LXRα (hLXRα) as an autoinducible gene. Induction in response to LXR ligands is observed in multiple human cell types including macrophages and occurs within 2–4 h. Analysis of the hLXRα promoter revealed three LXR response elements (LXREs); one exhibits strong affinity for both LXRα:RXR and LXRβ:RXR (a type I LXRE), and deletion and mutational studies indicate it plays a critical role in LXR-mediated induction. The other two LXREs are identical to each other, exist within highly conserved Alu repeats, and exhibit selective binding to LXRα:RXR (type II LXREs). In transfections, the type I LXRE acts as a strong mediator of both LXRα and LXRβ activity, whereas the type II LXRE acts as a weaker and selective mediator of LXRα activity. Our data suggest a model in which LXR ligands trigger an autoregulatory loop leading to selective induction of hLXRα gene expression. This would lead to increased hLXRα levels and transcription of its downstream target genes such as ABCA1, providing a simple yet exquisite mechanism for cells to respond to LXR ligands and cholesterol loading.

scholarly journals RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Kyuwon Lee ◽  
Hyeonju Yu ◽  
Stephanie Shouse ◽  
Byungwhi Kong ◽  
Jihye Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Global Gene Expression ◽  
Rna Seq ◽  
Knock Out ◽  
Forkhead Box M1 ◽  
Liver Injuries ◽  
Prohibitin 1 ◽  
Liver Tissues

Prohibitin 1 (PHB1) is an evolutionarily conserved and ubiquitously expressed protein that stabilizes mitochondrial chaperone. Our previous studies showed that liver-specific Phb1 deficiency induced liver injuries and aggravated lipopolysaccharide (LPS)-induced innate immune responses. In this study, we performed RNA-sequencing (RNA-seq) analysis with liver tissues to investigate global gene expression among liver-specific Phb1−/−, Phb1+/−, and WT mice, focusing on the differentially expressed (DE) genes between Phb1+/− and WT. When 78 DE genes were analyzed for biological functions, using ingenuity pathway analysis (IPA) tool, lipid metabolism-related genes, including insulin receptor (Insr), sterol regulatory element-binding transcription factor 1 (Srebf1), Srebf2, and SREBP cleavage-activating protein (Scap) appeared to be downregulated in liver-specific Phb1+/− compared with WT. Diseases and biofunctions analyses conducted by IPA verified that hepatic system diseases, including liver fibrosis, liver hyperplasia/hyperproliferation, and liver necrosis/cell death, which may be caused by hepatotoxicity, were highly associated with liver-specific Phb1 deficiency in mice. Interestingly, of liver disease-related 5 DE genes between Phb1+/− and WT, the mRNA expressions of forkhead box M1 (Foxm1) and TIMP inhibitor of metalloproteinase (Timp1) were matched with validation for RNA-seq in liver tissues and AML12 cells transfected with Phb1 siRNA. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated with hepatic Phb1.

scholarly journals RNA-Seq-Based Gene Expression Pattern and Morphological Alterations in Chick Thymus during Postnatal Development

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Zhouyiyuan Xue ◽  
Abdur Rahman Ansari ◽  
Xing Zhao ◽  
Kun Zang ◽  
Yu Liang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Postnatal Development ◽  
Expression Pattern ◽  
Expression Patterns ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Receptor Interaction ◽  
Rna Seq ◽  
Morphological Alterations

The thymus is a lobulated unique lymphoid immune organ that plays a critical role in the selection, development, proliferation, and differentiation of T cells. The thymus of developing chickens undergoes continued morphological alterations; however, the biomolecular and transcriptional dynamics of the postnatal thymus in avian species is not clear yet. Therefore, the thymuses from chickens at different stages of development (at weeks 0, 1, 5, 9, 18, and 27) were used in the present study. The RNA-seq method was used to study the gene expression patterns. On average, 24120819 clean reads were mapped, differentially expressed genes (DEGs) were identified on the basis of log values (fold change), including 744 upregulated and 425 downregulated genes. The expression pattern revealed by RNA-seq was validated by quantitative real-time PCR (qPCR) analysis of four important genes, which are PCNA, CCNA2, CCNB2, and CDK1. Thus, the current study revealed that during postnatal development, the thymus undergoes severe atrophy. Thymus structure was damaged and gene expression changed dramatically, especially at the 27th week of age. Moreover, we found significant changes of several signaling pathways such as the cytokine-cytokine receptor interaction and cell cycle signaling pathways. Hence, it may be inferred that those signaling pathways might be closely related to the postnatal chicken thymus development.

scholarly journals Single-Cell RNA-Seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-Deficiency

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A753-A754
Author(s):  
Jingfei Chen ◽  
Jialei Duan ◽  
Alina Montalbano ◽  
Boxun Li ◽  
Gary Hon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Immune Cell ◽  
Expression Patterns ◽  
Critical Role ◽  
Fetal Lung ◽  
Specific Gene ◽  
Rna Seq ◽  
Cell Clusters ◽  
Pregnant Mice

Abstract Single-cell RNA-seq of Mouse Decidual Leukocytes Reveals Intriguing Gestational Changes in the Immune Cell Landscape and Effects of SRC-1/-2 Double-DeficiencyOur previous findings suggest that the fetus signals the mother when it is ready to be born through secretion of surfactant components/immune modulators, surfactant protein A (SP-A) and platelet-activating factor (PAF) by the fetal lung into amniotic fluid (AF). This occurs with increased proinflammatory cytokine expression by fetal AF macrophages (Mϕ), increased myometrial NF-κB activation and contractile (CAP) gene expression. Steroid receptor coactivator (Src)-1 and Src-2 are critical for developmental induction SP-A and PAF by the fetal lung. The finding that pregnant wild-type (WT) mice carrying Src-1 and Src-2 double-deficient fetuses (Src-1/-2d/d) manifested a marked delay (~38h) in parturition, further suggests that signals for parturition arise from the fetus and that Src-1 and Src-2 serve a critical role. Infiltrating leukocytes at the maternal-fetal interface (MFI)/decidua are known to play a central role in pregnancy maintenance and parturition timing. However, there is limited knowledge regarding gestational changes in immune cell composition toward term. To analyze gestational changes in the composition of immune cells within decidua and effects of Src-1/-2d/d, we conducted single-cell RNA-seq of ~17,000 decidual leukocytes (CD45+) from pregnant mice at 15.5 and 18.5 dpc carrying WT or Src-1/-2d/d fetuses. Unsupervised clustering identified 22 distinct decidual immune cell clusters, comprised of Mϕ, B cells, natural killer cells, neutrophils, dendritic cells and monocytes. Significant differences in cell type composition and transcriptional profiles were found across study groups (WT @ 15.5 dpc vs. 18.5 dpc; Src-1/-2d/dvs. WT @15.5 dpc and 18.5 dpc). Interestingly, in deciduas of pregnant mice carrying WT fetuses, Mϕ and B cell clusters markedly increased between 15.5 and 18.5 dpc, whereas, neutrophils declined; however, these gestational changes did not occur in pregnant mice carrying Src-1/-2d/d fetuses. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these immune cell subtypes to uncover their putative functions. These findings highlight the complexity and dynamics of the decidual immune cell landscape during the transition from myometrial quiescence to contractility, and the fetal-maternal interactions leading to parturition. Support: NIH grants R01-HL050022 (CRM) and P01-HD087150 (CRM), Burroughs Wellcome Preterm Birth Grant #1019823 (CRM).

131 RNA-Seq TRANSCRIPTOME PROFILING OF INDIVIDUAL RHESUS MACAQUE OOCYTES AND PRE-IMPLANTATION EMBRYOS

2014 ◽  
Vol 26 (1) ◽  
pp. 179 ◽  
Author(s):  
J. L. Chitwood ◽  
V. R. Burruel ◽  
S. A. Meyers ◽  
P. J. Ross
Keyword(s):  
Gene Expression ◽  
Rhesus Macaque ◽  
Hierarchical Clustering ◽  
Intracytoplasmic Sperm Injection ◽  
Developmental Stages ◽  
Polar Body ◽  
Germinal Vesicle ◽  
Principal Component ◽  
Primate Species ◽  
Rna Seq

The objective of this study was to perform whole transcriptome sequencing (RNA-Seq) on individual rhesus macaque oocytes and intracytoplasmic sperm injection-derived embryos. Nine developmental stages were assayed (n = 2–3 per stage): germinal vesicle (GV), meiosis I (MI), and meiosis II (MII) oocytes and pronuclear (PN), 2-cell (2C), 4-cell (4C), 8-cell (8C), morula (MO), and blastocyst (BL) stage embryos. Rhesus females were superovulated with hrFSH and oocytes collected by follicular aspiration of ovaries recovered at necropsy 35 h after hCG treatment. Based on GV and polar body (PB) presence/absence, oocytes were classified as GV, MI, and MII. Embryos were produced by intracytoplasmic sperm injection of MII oocytes and cultured in HECM-9 media. Individual oocytes and embryos were collected at different developmental stages and frozen until use. The Clontech SMARTer Ultra Low Input RNA Kit for Illumina Sequencing was used for cDNA synthesis (oligo dT) and amplification. Sequencing libraries were created from fragmented cDNA with the Illumina TruSeq DNA kit. Single 100-bp reads were produced with a HiSEqn 2000 apparatus. Read alignment was done in CLC Genomics Workbench software to the RhesusBase genome annotation (53 788 genes). A gene was considered expressed if reads per kilobase of transcript model per million mapped reads (RPKM) was >0.4. Principal component analysis (PCA), hierarchical clustering, and differential gene expression analyses were performed with the DESEqn 2 package in R. On average, 22 311 310 reads were produced per sample with 63% aligning to the rhesus transcriptome. A total of 14 527 genes were detected in all replicates of at least one stage, with an average of 8855 genes per stage. The PCA and hierarchical clustering of all expressed genes discriminated between samples of different stages, except for 2C and PN, which were indistinguishable. All oocytes grouped to the same subcluster and close to PN-4C embryos, forming another subcluster. The 8C embryos constituted their own subcluster, which was closer to MO and BL than to other pre-implantation stages. Of genes expressed exclusively in embryo samples (n = 2823), 42% were expressed beginning at the 8C stage, 39% began expression at MO or BL, and 18% started expression between PN to 4C stage. The highest numbers of differentially expressed (DE) genes between consecutive stages were for MI-MII, MII-PN, 4C-8C, and 8C-MO, with an average of 5306 DE genes, whereas only 1060 were found in other comparisons. When gene expression was compared relative to the MII stage, 8C, MO, and BL had the highest numbers of DE genes (8965, 9635, and 9100, respectively, v. an average of 4713 for all other embryo stages). The high proportion of embryo-specific genes beginning expression at the 8C stage along with large numbers of DE genes observed between MII and 8C and the isolation of 8C samples to a unique expression cluster with PCA/hierarchical clustering indicates that major embryonic genome activation occurs at the 8C stage in the rhesus macaque. Overall, the dataset represents a comprehensive resource for analysis of polyadenylated transcript levels throughout early development in a nonhuman primate species.

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