Showing papers on "Gene expression published in 2009"
Journal Article•
TL;DR: In this article, a chromatin-immunoprecipitation-based microarray method (ChIP-chip) was used to locate promoters, enhancers and insulators in the human genome and investigate their roles in cell-type specific gene expression.
Abstract: The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression.
2,006 citations
TL;DR: In this analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.
Abstract: Synonymous mutations do not alter the encoded protein, but they can influence gene expression. To investigate how, we engineered a synthetic library of 154 genes that varied randomly at synonymous sites, but all encoded the same green fluorescent protein (GFP). When expressed in Escherichia coli, GFP protein levels varied 250-fold across the library. GFP messenger RNA (mRNA) levels, mRNA degradation patterns, and bacterial growth rates also varied, but codon bias did not correlate with gene expression. Rather, the stability of mRNA folding near the ribosomal binding site explained more than half the variation in protein levels. In our analysis, mRNA folding and associated rates of translation initiation play a predominant role in shaping expression levels of individual genes, whereas codon bias influences global translation efficiency and cellular fitness.
1,378 citations
TL;DR: The transition from the juvenile to the adult phase of shoot development in plants is accompanied by changes in vegetative morphology and an increase in reproductive potential, and the regulatory mechanism is described, which is mediated by sequentially operating miRNAs.
1,344 citations
TL;DR: The discovery that gene expression can be controlled by the Watson–Crick base-pairing of small RNAs with messenger RNAs containing complementary sequence — a process known as RNA interference — has markedly advanced the understanding of eukaryotic gene regulation and function.
Abstract: The discovery that gene expression can be controlled by the Watson–Crick base-pairing of small RNAs with messenger RNAs containing complementary sequence — a process known as RNA interference — has markedly advanced our understanding of eukaryotic gene regulation and function. The ability of short RNA sequences to modulate gene expression has provided a powerful tool with which to study gene function and is set to revolutionize the treatment of disease. Remarkably, despite being just one decade from its discovery, the phenomenon is already being used therapeutically in human clinical trials, and biotechnology companies that focus on RNA-interference-based therapeutics are already publicly traded.
1,196 citations
TL;DR: It is shown that themiR-17~92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis) and may serve as a valuable therapeutic target in the setting of ischemic disease.
Abstract: MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target messenger RNAs (mRNAs), leading to translational repression or degradation. Here, we show that the miR-17approximately92 cluster is highly expressed in human endothelial cells and that miR-92a, a component of this cluster, controls the growth of new blood vessels (angiogenesis). Forced overexpression of miR-92a in endothelial cells blocked angiogenesis in vitro and in vivo. In mouse models of limb ischemia and myocardial infarction, systemic administration of an antagomir designed to inhibit miR-92a led to enhanced blood vessel growth and functional recovery of damaged tissue. MiR-92a appears to target mRNAs corresponding to several proangiogenic proteins, including the integrin subunit alpha5. Thus, miR-92a may serve as a valuable therapeutic target in the setting of ischemic disease.
1,188 citations
TL;DR: It is reported here that expression of microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells (hESCs) but highly upregulated during differentiation, and a double-negative feedback loop involving OCT4, SOX2, KLF4, and miR- 145 is uncovered.
1,133 citations
TL;DR: Comparative studies on stress-responsive epigenomes and transcriptomes will enhance the understanding of stress adaptation of plants.
1,003 citations
TL;DR: It is demonstrated how SR proteins are emerging as one of the master regulators of gene expression as well as pivotal regulators of mRNA metabolism, and if these functions are disrupted, developmental defects or disease may result.
Abstract: The SR protein family comprises a number of phylogenetically conserved and structurally related proteins with a characteristic domain rich in arginine and serine residues, known as the RS domain. They play significant roles in constitutive pre-mRNA splicing and are also important regulators of alternative splicing. In addition they participate in post-splicing activities, such as mRNA nuclear export, nonsense-mediated mRNA decay and mRNA translation. These wide-ranging roles of SR proteins highlight their importance as pivotal regulators of mRNA metabolism, and if these functions are disrupted, developmental defects or disease may result. Furthermore, animal models have shown a highly specific, non-redundant role for individual SR proteins in the regulation of developmental processes. Here, we will review the current literature to demonstrate how SR proteins are emerging as one of the master regulators of gene expression.
988 citations
TL;DR: This Review focuses on cis-acting RNA localization elements, RNA-binding proteins, and the assembly of mRNAs into granules that are transported by molecular motors along cytoskeletal elements to their final destination in the cell.
972 citations
TL;DR: It is proposed that SIRT6 attenuatesNF-kappaB signaling via H3K9 deacetylation at chromatin, and hyperactive NF-kappB signaling may contribute to premature and normal aging.
963 citations
TL;DR: It is demonstrated that the mean expression value outperforms the current normalization strategy in terms of better reduction of technical variation and more accurate appreciation of biological changes.
Abstract: Gene expression analysis of microRNA molecules is becoming increasingly important. In this study we assess the use of the mean expression value of all expressed microRNAs in a given sample as a normalization factor for microRNA real-time quantitative PCR data and compare its performance to the currently adopted approach. We demonstrate that the mean expression value outperforms the current normalization strategy in terms of better reduction of technical variation and more accurate appreciation of biological changes.
TL;DR: Findings reveal that myosin genes not only encode the major contractile proteins of muscle, but act more broadly to influence muscle function by encoding a network of intronic miRNAs that control muscle gene expression and performance.
TL;DR: The results support a model in which variable exterior components feed into a large, densely connected core composed of ubiquitously expressed intracellular proteins.
Abstract: The parts of the genome transcribed by a cell or tissue reflect the biological processes and functions it carries out. We characterized the features of mammalian tissue transcriptomes at the gene level through analysis of RNA deep sequencing (RNA-Seq) data across human and mouse tissues and cell lines. We observed that roughly 8,000 protein-coding genes were ubiquitously expressed, contributing to around 75% of all mRNAs by message copy number in most tissues. These mRNAs encoded proteins that were often intracellular, and tended to be involved in metabolism, transcription, RNA processing or translation. In contrast, genes for secreted or plasma membrane proteins were generally expressed in only a subset of tissues. The distribution of expression levels was broad but fairly continuous: no support was found for the concept of distinct expression classes of genes. Expression estimates that included reads mapping to coding exons only correlated better with qRT-PCR data than estimates which also included 39 untranslated regions (UTRs). Muscle and liver had the least complex transcriptomes, in that they expressed predominantly ubiquitous genes and a large fraction of the transcripts came from a few highly expressed genes, whereas brain, kidney and testis expressed more complex transcriptomes with the vast majority of genes expressed and relatively small contributions from the most expressed genes. mRNAs expressed in brain had unusually long 39UTRs, and mean 39UTR length was higher for genes involved in development, morphogenesis and signal transduction, suggesting added complexity of UTR-based regulation for these genes. Our results support a model in which variable exterior components feed into a large, densely connected core composed of ubiquitously expressed intracellular proteins.
TL;DR: It is proposed that RNA granules can be both a cause and a consequence of altered mRNA translation, decay or editing and serve as key modulators of post-transcriptional and epigenetic gene expression.
Abstract: The composition of cytoplasmic messenger ribonucleoproteins (mRNPs) is determined by their nuclear and cytoplasmic histories and reflects past functions and future fates. The protein components of selected mRNP complexes promote their assembly into microscopically visible cytoplasmic RNA granules, including stress granules, processing bodies and germ cell (or polar) granules. We propose that RNA granules can be both a cause and a consequence of altered mRNA translation, decay or editing. In this capacity, RNA granules serve as key modulators of post-transcriptional and epigenetic gene expression.
TL;DR: The data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity, and identifies multiple expressive quantitative trait loci per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene.
Abstract: Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type-specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type-specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type-specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity.
TL;DR: A strategy to rapidly and efficiently isolate ribosome-associated mRNA transcripts from any cell type in vivo is described and the application of this technique is demonstrated in brain using neuron-specific Cre recombinase-expressing mice and in testis using a Sertoli cell Cre recomb inase- expressing mouse.
Abstract: Gene profiling techniques allow the assay of transcripts from organs, tissues, and cells with an unprecedented level of coverage. However, most of these approaches are still limited by the fact that organs and tissues are composed of multiple cell types that are each unique in their patterns of gene expression. To identify the transcriptome from a single cell type in a complex tissue, investigators have relied upon physical methods to separate cell types or in situ hybridization and immunohistochemistry. Here, we describe a strategy to rapidly and efficiently isolate ribosome-associated mRNA transcripts from any cell type in vivo. We have created a mouse line, called RiboTag, which carries an Rpl22 allele with a floxed wild-type C-terminal exon followed by an identical C-terminal exon that has three copies of the hemagglutinin (HA) epitope inserted before the stop codon. When the RiboTag mouse is crossed to a cell-type-specific Cre recombinase-expressing mouse, Cre recombinase activates the expression of epitope-tagged ribosomal protein RPL22ha, which is incorporated into actively translating polyribosomes. Immunoprecipitation of polysomes with a monoclonal antibody against HA yields ribosome-associated mRNA transcripts from specific cell types. We demonstrate the application of this technique in brain using neuron-specific Cre recombinase-expressing mice and in testis using a Sertoli cell Cre recombinase-expressing mouse.
TL;DR: This review will discuss recent literature on Nox protein tissue distribution, subcellular localization, activation, and the resulting signal transduction mechanisms.
TL;DR: A feedback mechanism mediated by general growth-dependent effects that does not require explicit gene regulation if the expressed protein affects cell growth is suggested that can lead to growth bistability and promote the acquisition of important physiological functions such as antibiotic resistance and tolerance.
TL;DR: Deep sequencing of Arabidopsis small RNAs revealed an increased abundance of TAS4-derived trans-acting small interfering RNAs (ta-siRNAs) in Pi-deficient shoots and uncovered an autoregulatory mechanism of PAP1/MYB75 via miR828 and Tas4-siR81(−) that regulates the biosynthesis of anthocyanin.
Abstract: Recent studies have demonstrated the important role of plant microRNAs (miRNAs) under nutrient deficiencies. In this study, deep sequencing of Arabidopsis (Arabidopsis thaliana) small RNAs was conducted to reveal miRNAs and other small RNAs that were differentially expressed in response to phosphate (Pi) deficiency. About 3.5 million sequence reads corresponding to 0.6 to 1.2 million unique sequence tags from each Pi-sufficient or Pi-deficient root or shoot sample were mapped to the Arabidopsis genome. We showed that upon Pi deprivation, the expression of miR156, miR399, miR778, miR827, and miR2111 was induced, whereas the expression of miR169, miR395, and miR398 was repressed. We found cross talk coordinated by these miRNAs under different nutrient deficiencies. In addition to miRNAs, we identified one Pi starvation-induced DICER-LIKE1-dependent small RNA derived from the long terminal repeat of a retrotransposon and a group of 19-nucleotide small RNAs corresponding to the 5' end of tRNA and expressed at a high level in Pi-starved roots. Importantly, we observed an increased abundance of TAS4-derived trans-acting small interfering RNAs (ta-siRNAs) in Pi-deficient shoots and uncovered an autoregulatory mechanism of PAP1/MYB75 via miR828 and TAS4-siR81(-) that regulates the biosynthesis of anthocyanin. This finding sheds light on the regulatory network between miRNA/ta-siRNA and its target gene. Of note, a substantial amount of miR399* accumulated under Pi deficiency. Like miR399, miR399* can move across the graft junction, implying a potential biological role for miR399*. This study represents a comprehensive expression profiling of Pi-responsive small RNAs and advances our understanding of the regulation of Pi homeostasis mediated by small RNAs.
TL;DR: Key features of the cell signaling and molecular regulatory mechanisms by which sex-dependent plasma GH patterns impart sex specificity to the liver are discussed, which provide novel insights into the physiological regulation of both xenobiotic and endobiotic metabolism.
Abstract: Sex differences in pharmacokinetics and pharmacodynamics characterize many drugs and contribute to individual differences in drug efficacy and toxicity. Sex-based differences in drug metabolism are the primary cause of sex-dependent pharmacokinetics and reflect underlying sex differences in the expression of hepatic enzymes active in the metabolism of drugs, steroids, fatty acids and environmental chemicals, including cytochromes P450 (P450s), sulfotransferases, glutathione transferases, and UDP-glucuronosyltransferases. Studies in the rat and mouse liver models have identified more than 1000 genes whose expression is sex-dependent; together, these genes impart substantial sexual dimorphism to liver metabolic function and pathophysiology. Sex differences in drug metabolism and pharmacokinetics also occur in humans and are due in part to the female-predominant expression of CYP3A4, the most important P450 catalyst of drug metabolism in human liver. The sexually dimorphic expression of P450s and other liver-expressed genes is regulated by the temporal pattern of plasma growth hormone (GH) release by the pituitary gland, which shows significant sex differences. These differences are most pronounced in rats and mice, where plasma GH profiles are highly pulsatile (intermittent) in male animals versus more frequent (nearly continuous) in female animals. This review discusses key features of the cell signaling and molecular regulatory mechanisms by which these sex-dependent plasma GH patterns impart sex specificity to the liver. Moreover, the essential role proposed for the GH-activated transcription factor signal transducer and activator of transcription (STAT) 5b, and for hepatic nuclear factor (HNF) 4α, as mediators of the sex-dependent effects of GH on the liver, is evaluated. Together, these studies of the cellular, molecular, and gene regulatory mechanisms that underlie sex-based differences in liver gene expression have provided novel insights into the physiological regulation of both xenobiotic and endobiotic metabolism.
TL;DR: The data suggest that gene expression changes during differentiation are programmed by chromatin modifications present at the HSC/HPC stage and provide a resource for enhancer and promoter identification.
TL;DR: The essential role of miR-19 is identified as the key oncogenic component of mir-17-92, both necessary and sufficient for promoting c-myc-induced lymphomagenesis by repressing apoptosis and implicate the functional diversity of miRNAs as the molecular basis for its pleiotropic effects during tumorigenesis.
Abstract: Recent studies have revealed the importance of multiple microRNAs (miRNAs) in promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent oncogenic activity. Genomic amplification and elevated expression of mir-17-92 occur in several human B-cell lymphomas, and enforced mir-17-92 expression in mice cooperates with c-myc to promote the formation of B-cell lymphomas. Unlike classic protein-coding oncogenes, mir-17-92 has an unconventional gene structure, where one primary transcript yields six individual miRNAs. Here, we functionally dissected the individual components of mir-17-92 by assaying their tumorigenic potential in vivo. Using the Em-myc model of mouse B-cell lymphoma, we identified miR-19 as the key oncogenic component of mir-17-92, both necessary and sufficient for promoting c-myc-induced lymphomagenesis by repressing apoptosis. The oncogenic activity of miR-19 is at least in part due to its repression of the tumor suppressor Pten. Consistently, miR-19 activates the Akt–mTOR (mammalian target of rapamycin) pathway, thereby functionally antagonizing Pten to promote cell survival. Our findings reveal the essential role of miR-19 in mediating the oncogenic activity of mir-17-92, and implicate the functional diversity of mir-17-92 components as the molecular basis for its pleiotropic effects during tumorigenesis.
TL;DR: This work constitutes the first report describing changes in miR expression in response to IR in the mouse heart, showing that miR-21 regulates MMP-2 expression in CFs of the infarct zone via a PTEN pathway.
Abstract: Aims MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level by either degradation or translational repression of a target mRNA. Encoded in the genome of most eukaryotes, miRNAs have been proposed to regulate specifically up to 90% of human genes through a process known as miRNA-guided RNA silencing. For the first time, we sought to test how myocardial ischaemia–reperfusion (IR) changes miR expression.
Methods and results Following 2 and 7 h of IR or sham operation, myocardial tissue was collected and subjected to miRNA expression profiling and quantification using a Bioarray system that screens for human-, mice-, rat-, and Ambi-miR. Data mining and differential analyses resulted in 13 miRs that were up-regulated on day 2, 9 miRs that were up-regulated on day 7, and 6 miRs that were down-regulated on day 7 post-IR. Results randomly selected from expression profiling were validated using real-time PCR. Tissue elements laser-captured from the infarct site showed marked induction of miR-21. In situ hybridization studies using locked nucleic acid miR-21-specific probe identified that IR-inducible miR-21 was specifically localized in the infarct region of the IR heart. Immunohistochemistry data show that cardiac fibroblasts (CFs) are the major cell type in the infarct zone. Studies with isolated CFs demonstrated that phosphatase and tensin homologue (PTEN) is a direct target of miR-21. Modulation of miR-21 regulated expression of matrix metalloprotease-2 (MMP-2) via a PTEN pathway. Finally, we noted a marked decrease in PTEN expression in the infarct zone. This decrease was associated with increased MMP-2 expression in the infarct area.
Conclusion This work constitutes the first report describing changes in miR expression in response to IR in the mouse heart, showing that miR-21 regulates MMP-2 expression in CFs of the infarct zone via a PTEN pathway.
TL;DR: Overexpression of Zc3h12a accelerated Il6 mRNA degradation via its 3′-untranslated region (UTR), and destabilized RNAs with3′-UTRs for genes including Il6, Il12p40 and the calcitonin receptor gene Calcr indicate that Zc 3h 12a is an essential RNase that prevents immune disorders by directly controlling the stability of a set of inflammatory genes.
Abstract: Toll-like receptors (TLRs) recognize microbial components, and evoke inflammation and immune responses. TLR stimulation activates complex gene expression networks that regulate the magnitude and duration of the immune reaction. Here we identify the TLR-inducible gene Zc3h12a as an immune response modifier that has an essential role in preventing immune disorders. Zc3h12a-deficient mice suffered from severe anaemia, and most died within 12 weeks. Zc3h12a(-/-) mice also showed augmented serum immunoglobulin levels and autoantibody production, together with a greatly increased number of plasma cells, as well as infiltration of plasma cells to the lung. Most Zc3h12a(-/-) splenic T cells showed effector/memory characteristics and produced interferon-gamma in response to T-cell receptor stimulation. Macrophages from Zc3h12a(-/-) mice showed highly increased production of interleukin (IL)-6 and IL-12p40 (also known as IL12b), but not TNF, in response to TLR ligands. Although the activation of TLR signalling pathways was normal, Il6 messenger RNA decay was severely impaired in Zc3h12a(-/-) macrophages. Overexpression of Zc3h12a accelerated Il6 mRNA degradation via its 3'-untranslated region (UTR), and destabilized RNAs with 3'-UTRs for genes including Il6, Il12p40 and the calcitonin receptor gene Calcr. Zc3h12a contains a putative amino-terminal nuclease domain, and the expressed protein had RNase activity, consistent with a role in the decay of Il6 mRNA. Together, these results indicate that Zc3h12a is an essential RNase that prevents immune disorders by directly controlling the stability of a set of inflammatory genes.
TL;DR: The mRNA decay rates presented in this report are the largest data set for mammals and the first for ES cells and the stability of mRNAs correlated more significantly with the structural features of genes than the function of genes.
Abstract: Degradation of mRNA is one of the key processes that control the steady-state level of gene expression. However, the rate of mRNA decay for the majority of genes is not known. We successfully obtained the rate of mRNA decay for 19 977 non-redundant genes by microarray analysis of RNA samples obtained from mouse embryonic stem (ES) cells. Median estimated half-life was 7.1 h and only <100 genes, including Prdm1, Myc, Gadd45 g, Foxa2, Hes5 and Trib1, showed half-life less than 1 h. In general, mRNA species with short half-life were enriched among genes with regulatory functions (transcription factors), whereas mRNA species with long half-life were enriched among genes related to metabolism and structure (extracellular matrix, cytoskeleton). The stability of mRNAs correlated more significantly with the structural features of genes than the function of genes: mRNA stability showed the most significant positive correlation with the number of exon junctions per open reading frame length, and negative correlation with the presence of PUF-binding motifs and AU-rich elements in 3′-untranslated region (UTR) and CpG di-nucleotides in the 5′-UTR. The mRNA decay rates presented in this report are the largest data set for mammals and the first for ES cells.
TL;DR: It is reported that mouse genes tend to express mRNAs with longer 3′ UTRs as embryonic development progresses, and it is suggested that lengthening of 3″ UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.
Abstract: The 3′ untranslated regions (3′ UTRs) of mRNAs contain cis-acting elements for posttranscriptional regulation of gene expression. Here, we report that mouse genes tend to express mRNAs with longer 3′ UTRs as embryonic development progresses. This global regulation is controlled by alternative polyadenylation and coordinates with initiation of organogenesis and aspects of embryonic development, including morphogenesis, differentiation, and proliferation. Using myogenesis of C2C12 myoblast cells as a model, we recapitulated this process in vitro and found that 3′ UTR lengthening is likely caused by weakening of mRNA polyadenylation activity. Because alternative 3′ UTR sequences are typically longer and have higher AU content than constitutive ones, our results suggest that lengthening of 3′ UTR can significantly augment posttranscriptional control of gene expression during embryonic development, such as microRNA-mediated regulation.
TL;DR: Overall, these data suggest that TLR4-activated NF-κB rapidly increases the expression of miR-9 that operates a feedback control of the NF-σκB-dependent responses by fine tuning theexpression of a key member of theNF-κBs family.
Abstract: Inflammation involves a coordinated, sequential, and self limiting sequence of events controlled by positive and negative regulatory mechanisms. Recent studies have shown that microRNAs (miRNAs), an evolutionarily conserved class of endogenous 22-nucleotide noncoding RNAs, contribute to the regulation of inflammation by repressing gene expression at the posttranscriptional level. In this study, we characterize the profile of miRNAs induced by LPS in human polymorphonuclear neutrophils (PMN) and monocytes. In particular, we identify miR-9 as the only miRNA (among 365 analyzed) up-regulated in both cell types after TLR4 activation. miR-9 is also induced by TLR2 and TLR7/8 agonists and by the proinflammatory cytokines TNF-α and IL-1β, but not by IFNγ. Among the 3 different genes encoding miR-9 precursors in humans, we show that LPS selectively induces the transcription of miR-9–1 located in the CROC4 locus, in a MyD88- and NF-κB-dependent manner. In PMN and monocytes, LPS regulates NFKB1 at both the transcriptional and posttranscriptional levels, and a conserved miR-9 seed sustained a miR-9-dependent inhibition of the NFKB1 transcript. Overall, these data suggest that TLR4-activated NF-κB rapidly increases the expression of miR-9 that operates a feedback control of the NF-κB-dependent responses by fine tuning the expression of a key member of the NF-κB family.
TL;DR: The transcriptional landscapes of prefrontal cortex and perisylvian speech and language areas are characterized, which exhibit a population-level global expression symmetry and it is shown that differentially expressed genes are more frequently associated with human-specific evolution of putative cis-regulatory elements.
TL;DR: This study provides an in silico dataset for recognition of differentially expressed genes at the cell-, region-, and organ-specific levels.
Abstract: Multicellular organs are composed of distinct cell types with unique assemblages of translated mRNAs. Here, ribosome-associated mRNAs were immunopurified from specific cell populations of intact seedlings using Arabidopsis thaliana lines expressing a FLAG-epitope tagged ribosomal protein L18 (FLAG-RPL18) via developmentally regulated promoters. The profiling of mRNAs in ribosome complexes, referred to as the translatome, identified differentially expressed mRNAs in 21 cell populations defined by cell-specific expression of FLAG-RPL18. Phloem companion cells of the root and shoot had the most distinctive translatomes. When seedlings were exposed to a brief period of hypoxia, a pronounced reprioritization of mRNA enrichment in the cell-specific translatomes occurred, including a ubiquitous rise in 49 mRNAs encoding transcription factors, signaling proteins, anaerobic metabolism enzymes, and uncharacterized proteins. Translatome profiling also exposed an intricate molecular signature of transcription factor (TF) family member mRNAs that was markedly reconfigured by hypoxia at global and cell-specific levels. In addition to the demonstration of the complexity and plasticity of cell-specific populations of ribosome-associated mRNAs, this study provides an in silico dataset for recognition of differentially expressed genes at the cell-, region-, and organ-specific levels.
TL;DR: It is shown that HIF1 regulates the expression of mir-210 in a variety of tumor types through a hypoxia-responsive element, suggesting an important role for mir- 210 in regulating the hypoxic response of tumor cells and tumor growth.