Biology subjects

Li, C.

Publications and source records attributed to Li, C..

At least 973 records · Page 54Linked to original sources

bioRxiv2020

Exploring the Pharmacological Mechanism of Bezoar on Cerebral Ischemic Stroke using a Network Pharmacology Approach

BackgroundIschemic stroke is a common clinical disease limited by its time window for treatment. In addition to its high mortality rate, only one treatment currently exists for ischemic stroke. Nonetheless, traditional Chinese medicine is often used as a reatment for the disease. Bezoar is a multi-functional drug that has been demonstrated to be effective for the treatment of ischemic stroke. However, its mechanism of action is yet to be fully elucidated. Based on network pharmacology, we explored the potential mechanism of action of bezoar. Symmap and literature data mining methods were used to obtain the target of bezoar. The mechanism of bezoar for the treatment of ischemic stroke was identified and ischemic stroke-related targets were retrieved using DrugBank, Online Mendelian Inheritance in Man, and Therapeutic Target Database. Protein-protein interaction networks were constructed using the Cytoscape plugin, BisoGenet, and analysed by topological methods. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment were carried out via the Database for Annotation, Visualization, and Integrated Discovery server. We obtained 48 potential targets and 3 signalling pathways, including mitogen-activated protein kinase, hypoxia-inducible factor-1, and tumour necrosis factor signalling pathways. The mechanism of action of bezoar on ischemic stroke involves multiple targets and signalling pathways. Our research provides a network pharmacology framework for future Chinese medicinal research.

neuroscience↗

bioRxiv2020

Tissue-resident CD4+ T helper cells assist protective respiratory mucosal B and CD8+ T cell memory responses

The roles of CD4+ T helper cells (TH) in shaping localized memory B and CD8+ T cell immunity in the mucosal tissues are largely unexplored. Here, we report that lung TH cells provide local assistance for the optimal development of tissue-resident memory B (BRM) and CD8+ T (TRM) cells following the resolution of primary influenza virus infection. We identify a population of tissue-resident CD4+ TH (aka TRH) cells that co-exhibit follicular T helper (TFH) and TRM cell features and mediate local help of CD4+ T cells to B and CD8+ T cells. Optimal TRH cell formation requires lung B cells and transcription factors involved in TFH or TRM development. Further, we show that TRH cells deliver local help to B and CD8 T cells through CD40L and IL-21-dependent mechanisms. Our data have uncovered a new tissue-resident TH cell population that is specialized in assisting the development of mucosal protective B and CD8+ T cell responses in situ.

immunology↗

bioRxiv2020

TRIBE editing reveals specific mRNA targets of eIF4E-BP in Drosophila and in mammals

4E-BP (eIF4E-BP) represses translation initiation by binding to the 5cap-binding protein eIF4E and inhibiting its activity. Although 4E-BP has been shown to be important in growth control, stress response, cancer, neuronal activity and mammalian circadian rhythms, it is not understood how it preferentially represses a subset of mRNAs. We successfully used hyperTRIBE (Targets of RNA-binding proteins identified by editing) to identify in vivo 4E-BP mRNA targets in both Drosophila and mammals under conditions known to activate 4E-BP. The protein associates with specific mRNAs, and ribosome profiling data show that mTOR inhibition changes the translational efficiency of 4E-BP TRIBE targets compared to non-targets. In both systems, these targets have specific motifs and are enriched in translation-related pathways, which correlate well with the known activity of 4E-BP and suggest that it modulates the binding specificity of eIF4E and contributes to mTOR translational specificity.

molecular biology↗

bioRxiv2020

Genome-wide Identification and Analysis of Enhancer Regulated microRNAs Across 31 Human Tissues

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner and dysregulation in various diseases such as cancer. Recent studies showed that enhancers can regulate miRNAs and participate in the biological synthesis of miRNAs. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited significant tissue-specific feature and there was a noteworthy positive correlation between the expression of miRNA and the number of regulated enhancers in most tissues. Furthermore, it was found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of eRNAs whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, GC content and histone modification signatures. Notably, GC content, H3K4me1, H3K36me3 were present differently between distal regulation and proximal regulation, suggesting they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507[~]miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on enhancer affected the expression TNFRSF18 gene as a tumor suppressor.

bioinformatics↗

bioRxiv2020

Tracing the origin of a new organ by inferring the genetic basis of rumen evolution

The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of microorganisms that facilitates efficient digestion of plant fibers. We used 897 transcriptomes from three Cetartiodactyla lineages: ruminants, camels and cetaceans, as well as data from ruminant comparative genomics and functional assays to explore the genetic basis of rumen origin and evolution. Comparative analyses reveal that the rumen and the first-chamber stomachs of camels and cetaceans shared a common tissue origin from the esophagus. The rumen recruited genes from other tissues/organs and up-regulated many esophagus genes to aquire functional innovations involving epithelium absorption, improvement of the ketone body metabolism and regulation of microbial community. These innovations involve such genetic changes as ruminant-specific conserved elements, newly evolved genes and positively selected genes. Our in vitro experiements validate the functions of one enhancer, one positively selected gene and two newly evolved antibacterial genes. Our study provides novel insights into the origin and evolution of a complex organ.

evolutionary biology↗

bioRxiv2020

Exon probe sets and bioinformatics pipelines for all levels of fish phylogenomics

Exon markers have a long history of use in phylogenetics of ray-finned fishes, the most diverse clade of vertebrates with more than 35,000 species. As the number of published genomes increases, it has become easier to test exons and other genetic markers for signals of ancient duplication events and filter out paralogs that can mislead phylogenetic analysis. We present seven new probe sets for current target-capture phylogenomic protocols that capture 1,104 exons explicitly filtered for paralogs using gene trees. These seven probe sets span the diversity of teleost fishes, including four sets that target five hyper-diverse percomorph clades which together comprise ca. 17,000 species (Carangaria, Ovalentaria, Eupercaria, and Syngnatharia + Pelagiaria combined). We additionally included probes to capture exon markers that have been commonly used in fish phylogenetics, despite some being flagged for paralogs, to facilitate integration of old and new molecular phylogenetic matrices. We tested these probes and merged new exon-capture sequence data into an existing data matrix of 1,105 exons and 300 ray-finned fish species. We provide an optimized bioinformatics pipeline to assemble exon capture data from raw reads to alignments for downstream analysis. We show that loci with known paralogs are at risk of assembling duplicated sequences with target-capture, but we also assembled many useful orthologous sequences. These probe sets are a valuable resource for advancing fish phylogenomics because they can be easily extracted from increasingly available whole genome and transcriptome datasets, and also may be integrated with existing PCR-based exon and mitochondrial datasets.

evolutionary biology↗

bioRxiv2020

Cross-platform genetic discovery of small molecule products of metabolism and application to clinical outcomes

Circulating levels of small molecules or metabolites are highly heritable, but the impact of genetic differences in metabolism on human health is not well understood. In this cross-platform, genome-wide meta-analysis of 174 metabolite levels across six cohorts including up to 86,507 participants (70% unpublished data), we identify 499 (362 novel) genome-wide significant associations (p<4.9×10-10) at 144 (94 novel) genomic regions. We show that inheritance of blood metabolite levels in the general population is characterized by pleiotropy, allelic heterogeneity, rare and common variants with large effects, non-linear associations, and enrichment for nonsynonymous variation in transporter and enzyme encoding genes. The majority of identified genes are known to be involved in biochemical processes regulating metabolite levels and to cause monogenic inborn errors of metabolism linked to specific metabolites, such as ASNS (rs17345286, MAF=0.27) and asparagine levels. We illustrate the influence of metabolite-associated variants on human health including a shared signal at GLP2R (p.Asp470Asn) associated with higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes risk, and demonstrate beta-arrestin signalling as the underlying mechanism in cellular models. We link genetically-higher serine levels to a 95% reduction in the likelihood of developing macular telangiectasia type 2 [odds ratio (95% confidence interval) per standard deviation higher levels 0.05 (0.03-0.08; p=9.5×10-30)]. We further demonstrate the predictive value of genetic variants identified for serine or glycine levels for this rare and difficult to diagnose degenerative retinal disease [area under the receiver operating characteristic curve: 0.73 (95% confidence interval: 0.70-0.75)], for which low serine availability, through generation of deoxysphingolipids, has recently been shown to be causally relevant. These results show that integration of human genomic variation with circulating small molecule data obtained across different measurement platforms enables efficient discovery of genetic regulators of human metabolism and translation into clinical insights.Competing Interest StatementA.S.B. has received grants from AstraZeneca, Biogen, Bioverativ, Merck, Novartis, and Sanofi. J. D. sits on the International Cardiovascular and Metabolic Advisory Board for Novartis (since 2010), the Steering Committee of UK Biobank (since 2011), the MRC International Advisory Group (ING) member, London (since 2013), the MRC High Throughput Science Omics Panel Member, London (since 2013), the Scientific Advisory Committee for Sanofi (since 2013), the International Cardiovascular and Metabolism Research and Development Portfolio Committee for Novartis and the Astra Zeneca Genomics Advisory Board (2018). E.B.F. is an employee and stock holder of Pfizer.View Full Text

genetics↗

bioRxiv2020

Thermogenic hydrocarbons sustain diverse subseafloor microbial communities in deep sea cold seep sediments

At marine cold seeps, gaseous and liquid hydrocarbons migrate from deep subsurface origins to the sediment-water interface. Cold seep sediments are known to host taxonomically diverse microorganisms, but little is known about their metabolic potential and depth distribution in relation to hydrocarbon and electron acceptor availability. In this work, we combined geochemical, metagenomic and metabolomic measurements in distinct sediment redox regimes to profile microbial activities within the uppermost 350 cm of a newly discovered cold seep in the NW Atlantic deep sea (2.3 km water depth). Depth-resolved metagenomic profiling revealed compositional and functional differentiation between near-surface sediments (dominated by Proteobacteria) and deeper subsurface layers (dominated by Atribacteria, Chloroflexi, Euryarchaeota and Lokiarchaeota). Metabolic capabilities of community members were inferred from 376 metagenome-assembled genomes spanning 46 phyla (including five novel candidate phyla). In deeper sulfate-reducing and methanogenic sediments, various community members are capable of anaerobically oxidizing short-chain alkanes (alkyl-CoM reductase pathway), longer-chain alkanes (fumarate addition pathway), and aromatic hydrocarbons (fumarate addition and subsequent benzoyl-CoA pathways). Geochemical profiling demonstrated that hydrocarbon substrates are abundant in this location, thermogenic in origin, and subject to biodegradation. The detection of alkyl-/arylalkylsuccinate metabolites, together with carbon isotopic signatures of ethane, propane and carbon dioxide, support that microorganisms are actively degrading hydrocarbons in these sediments. Hydrocarbon oxidation pathways operate alongside other deep seabed metabolisms such as sulfide oxidation, hydrogen oxidation, carbon fixation, fermentation and reductive dehalogenation. Upward migrated thermogenic hydrocarbons thus sustain diverse microbial communities with activities that affect subseafloor biogeochemical processes across the redox spectrum in deep sea cold seeps.

microbiology↗

bioRxiv2020

Effects of rhein on bile acid homeostasis in rats

Rhein, the active ingredient of rhubarb, a medicinal and edible plant, is widely used in clinical practice. In this work, we investigated the alterations of 14 bile acids and hepatic transporters after rats were administered rhein for 5 consecutive weeks. There was no obvious injury to the liver and kidney, and there were no significant changes in biochemical indicators. However, 1,000 mg/kg rhein increased the liver total bile acid (TBA) levels, especially taurine-conjugated bile acids (t-CBAs), inhibited the expression of Farnesoid X receptor (FXR) and (bile salt export pump) BSEP mRNA, and upregulated the expression of (cholesterol 7-hydroxylase) CYP7A1 mRNA. Rhein close to the clinical dose reduced the amounts of TBAs, especially unconjugated bile acids (UCBAs), and elevated the expression of FXR and multidrug resistance-associated protein 3 (Mrp3) mRNA. These results denote that rhein is not toxic and is safe to use at a reasonable dose and timing.

pharmacology and toxicology↗

bioRxiv2020

Quantitative in vivo analyses reveal a complex pharmacogenomic landscape in lung adenocarcinoma

AbstractThe lack of knowledge about the relationship between tumor genotypes and therapeutic responses remains one of the most important gaps in enabling the effective use of cancer therapies. Here, we couple a multiplexed and quantitative platform with robust statistical methods to enable pharmacogenomic mapping of lung cancer treatment responses in vivo. We uncover a surprisingly complex map of genotype-specific therapeutic responses, with over 20% of possible interactions showing significant resistance or sensitivity. We validate one of these interactions - the resistance of Keap1 mutant tumors to platinum therapy - using a large patient response dataset. Our results highlight the importance of understanding the genetic determinants of treatment responses in the development of precision therapies and define a strategy to identify such determinants.

cancer biology↗

bioRxiv2020

WISP2/CCN5 gene knockdown in vitro and in vivo exhibits proliferation promotion of breast cancer through targeting Skp2 and p27Kip1

BackgroundEmerging evidence has demonstrated that WISP2/CCN5 is critically involved in tumorigenesis. However, the function of WISP2/CCN5 in breast cancer carcinogenesis is largely unclear. Methodswe aim to explore the effects and potential mechanisms of WISP2/CCN5 on proliferation of breast cancer cells and carcinogenesis of breast cancer xenograft. Lentivirus vector with WISP2/CCN5shRNA was transfected into MCF-7, and breast cancer cells and xenograft were conducted. Effect of WISP2/CCN5 on growth and carcinogenesis of breast cancer cells and xenografts was evaluated by MTT assay and tumor volume. The relationship between WISP2/CCN5, Skp2 and p27Kip1 was detected in vitro and in vivo by RT-PCR at mRNA level and Western blotting at protein level. ResultsThe result of MTT assay indicated that MCF-7 cell growth viability in WISP2/CCN5 gene knockdown group was significantly higher than negative vector group(P<0.05) or control group (P<0.05). It suggested that knockdown of WISP2/CCN5 gene by shRNA lentivirus plasmid promoted proliferation of MCF-7 cells. The growth curves of breast cancer xenograft showed that xenografts in WISP2/CCN5 knockdown group grew more quickly than negative vector group(P< 0.05) or control group (P< 0.05). Subsequently, the results of RT-PCR and Western blotting revealed that WISP2/CCN5 gene knockdown led to increased Skp2 and decreased p27Kip1 at mRNA and protein levels. WISP2/CCN5 exerts its inhibition on proliferation of MCF-7 cell line and suppressive functions on growth of breast carcinoma via regulation of Skp2 and p27Kip1at mRNA and protein levels. However, WISP2/CCN5 gene knockdown resulted in loss of inhibition effect on MCF-7 and breast cancer. ConclusionsOur findings suggest that WISP2/CCN5 could be a useful therapeutic strategy for the treatment of breast cancer through targeting Skp2 and p27Kip1.

molecular biology↗

bioRxiv2020

Genetic diversity and evolution of Hantaan virus in China and its neighbors

BackgroudHantaan virus (HTNV), as one of the pathogenic hantaviruses of HFRS, has raised serious concerns in Eurasia. China and its neighbors, especially Russia and South Korea, are seriously suffered HTNV infections. Recent studies reported genetic diversity and phylogenetic features of HTNV in different parts of China, but the analyses from the holistic perspective are rare. Methodology and Principal FindingsTo better understand HTNV genetic diversity and dynamics, we analyzed all available complete sequences derived from the S and M segments with bio-informatic tools. Our study revealed 11 phylogroups and sequences showed obvious geographic clustering. We found 42 significant amino acid variants sites and 18 of them located in immune epitopes. Nine recombination events and seven reassortment isolates were deteced in our study. Sequences from Guizhou were highly genetic divergent, characterized by the emergence of multiple lineages, recombination and reassortment events. We found that HTNV probably emerged in Zhejiang about 1,000 years ago and the population size expanded from 1980s to 1990s. Bayesian stochastic search variable selection analysis revealed that Heilongjiang, Shaanxi and Guizhou played important roles in HTNV evolution and migration. Conclusions/SignificanceThese findings reveal the original and evolution features of HTNV which might assist in understanding Hantavirus epidemics and would be useful for disease prevention and control. Author summaryHemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS) are endemic zoonotic infectious diseases caused by hantaviruses that belong to the Family Bunyaviridae. Hantaviruses have gained worldwide attention as etiological agents of emerging zoonotic diseases, with fatality rates ranging from <10% up to 60%. However, our knowledge about the emergence and evolution of HTNV is limited. To get more information about HTNV genetic diversity and phylogenetic features in holistic perspective, we investigated the genetic diversity and spatial distribution of HTNV using all available whole genomic sequences of S and M segments. We also gain insights into the genetic diversity and spatial-temporal dynamics of HTNV. These data can augment traditional approach to infectious disease surveillance and control.

evolutionary biology↗

bioRxiv2020

Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody

The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 800 laboratory-confirmed human infections, including 25 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. Considering the relatively high identity of receptor binding domain (RBD) in 2019-nCoV and SARS-CoV, it is urgent to assess the cross-reactivity of anti-SARS-CoV antibodies with 2019-nCoV spike protein, which could have important implications for rapid development of vaccines and therapeutic antibodies against 2019-nCoV. Here, we report for the first time that a SARS-CoV-specific human monoclonal antibody, CR3022, could bind potently with 2019-nCoV RBD (KD of 6.3 nM). The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. Therefore, CR3022 has the potential to be developed as candidate therapeutics, alone or in combination with other neutralizing antibodies, for the prevention and treatment of 2019-nCoV infections. Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g., m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, indicating that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.

microbiology↗

bioRxiv2020

SnpReady for Rice (SR4R) Database

The information commons for rice (IC4R) database is a collection of [~]18 million SNPs (single nucleotide polymorphisms) identified by the resequencing of 5,152 rice accessions. Although IC4R offers ultra-high density rice variation map, these raw SNPs are not readily usable for the public. To satisfy different research utilizations of SNPs for population genetics, evolutionary analysis, association studies and genomic breeding in rice, the raw genotypic data of the 18 million SNPs were processed by unified bioinformatics pipelines. The outcomes were used to develop a daughter database of IC4R - SnpReady for Rice (SR4R). The SR4R presents four reference SNP panels, including 2,097,405 hapmapSNPs after data filtration and genotype imputation, 156,502 tagSNPs selected from linkage disequilibrium (LD)-based redundancy removal, 1,180 fixedSNPs selected from genes exhibiting selective sweep signatures, and 38 barcodeSNPs selected from DNA fingerprinting simulation. SR4R thus offers a highly efficient rice variation map that combines reduced SNP redundancy with extensive data describing the genetic diversity of rice populations. In addition, SR4R provides rice researchers with a web-interface that enables them to browse all four SNP panels, use online toolkits, and retrieve the original data and scripts for a variety of population genetics analyses on local computers. The SR4R is freely available to academic users at http://sr4r.ic4r.org/.

bioinformatics↗

bioRxiv2020

Moderating Effect of Social Support on Role Conflict and Job Satisfaction Among Nurses with Multiple Roles

Registered nurses perform multiple roles in their lives at work, at home, and at school when they decide to pursue various types of advanced degrees. Work-family conflict was found to be negatively correlated with job satisfaction among nurses. This study aimed to determine the moderating effect of social support on the relationship between role conflicts and job satisfaction among registered nurses in mainland China. The study had a cross-sectional correlational design. Convenience sampling was applied to recruit 320 nurses with multiple roles from 8 nursing universities and 3 hospitals in China between January and August 2017. SPSS (version 20.0) software and PROCESS program was used to examine to moderating effect of social support between the relationship of role conflicts and job satisfaction. It was found that role conflicts were negatively correlated with job satisfaction. Support from work and support from family negatively moderated the relationship between role conflicts and job satisfaction. These findings suggest that support from family, coworkers and nursing administrators, and the implementation of school- and family-friendly policies would help nurses who are pursuing further nursing degrees to handle their multiple roles and improve their job satisfaction.

scientific communication and education↗

bioRxiv2020

Millipede genomes reveal unique adaptation of genes and microRNAs during myriapod evolution

The Myriapoda including millipedes and centipedes is of major importance in terrestrial ecology and nutrient recycling. Here, we sequenced and assembled two chromosomal-scale genomes of millipedes Helicorthomorpha holstii (182 Mb, N50 18.11 Mb mainly on 8 pseudomolecules) and Trigoniulus corallinus (449 Mb, N50 26.78 Mb mainly on 15 pseudomolecules). Unique defense systems, genomic features, and patterns of gene regulation in millipedes, not observed in other arthropods, are revealed. Millipedes possesses a unique ozadene defensive gland unlike the venomous forcipules in centipedes. Sets of genes associated with anti-microbial activity are identified with proteomics, suggesting that the ozadene gland is not primarily an antipredator adaptation (at least in T. corallinus). Macro-synteny analyses revealed highly conserved genomic blocks between centipede and the two millipedes. Tight Hox and the first loose ecdysozoan ParaHox homeobox clusters are identified, and a myriapod-specific genomic rearrangement including Hox3 is also observed. The Argonaute proteins for loading small RNAs are duplicated in both millipedes, but unlike insects, an argonaute duplicate has become a pseudogene. Evidence of post-transcriptional modification in small RNAs, including species-specific microRNA arm switching that provide differential gene regulation is also obtained. Millipede genomes reveal a series of unique genomic adaptations and microRNA regulation mechanisms have occurred in this major lineage of arthropod diversity. Collectively, the two millipede genomes shed new light on this fascinating but poorly understood branch of life, with a highly unusual body plan and novel adaptations to their environment.

evolutionary biology↗

bioRxiv2020

Single cell atlas of trisomy 21 cerebral cortex

Down syndrome (DS) is one of the most common human birth defects caused by trisomy 21 (T21), leading to a variety of cognitive impairments. The cellular composition of human brain has been explored using single cell RNA sequencing in both physiological and pathological conditions. However, the cellular heterogeneity of human brain with chromosome aneuploidy is largely unknown. Here, we profiled the transcriptome of 36046 cells in cerebral cortex of T21 human fetus, covering frontal lobe, parietal lobe, occipital lobe and temporal lobe. Intriguingly, we detected several genes positively associated with neurons maturation was dysregulated in T21 frontal cortex (HIC2, POU2F2, ZGLP1 and FOXK1). To share, explore and utilized the data resources of T21 cerebral cortex, we developed a comprehensive platform named T21atlas, composing of two functional modules (T21cluster and T21talk). Overall, our study provides, as far as we know, the first single cell atlas for T21 cerebral cortex, which could promote our understanding of the molecular mechanism of DS at an unprecedented resolution and could potentially facilitate the development of novel clinical therapeutics against T21.

neuroscience↗

bioRxiv2019

Transcription levels of a long noncoding RNA orchestrate opposing regulatory and cell fate outcomes in yeast

Many long noncoding RNAs (lncRNAs) act in cis through transcription-coupled chromatin alterations that drive changes in local gene expression. How some cis-acting lncRNAs promote and others repress gene expression remains poorly understood. Here we report that in S. cerevisiae transcription levels of the lncRNA IRT2, located upstream in the promoter of the inducer of meiosis gene, regulate opposing chromatin and transcription states. Low IRT2 transcription displays enhancer RNA-like features. At these levels, IRT2 promotes histone exchange delivering acetylated histone H3 lysine 56 to chromatin thereby facilitating recruitment of a transcription factor and consequently activating transcription. Conversely, increasing IRT2 transcription enhances chromatin assembly and transcriptional repression. The opposing functions of IRT2 direct a regulatory circuit, which ensures that cells expressing opposite, but not one of either, mating-type loci enter meiosis. Our data demonstrate that the transcription levels of an lncRNA are key to controlling gene expression and cell fate outcomes.

biochemistry↗