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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

Transcription drives DNA replication initiation and termination in human cells

The locations of active DNA replication origins in the human genome, and the determinants of origin activation, remain controversial. Additionally, neither the predominant sites of replication termination nor the impact of transcription on replication-fork mobility have been defined. We demonstrate that replication initiation occurs preferentially in the immediate vicinity of the transcription start site of genes occupied by high levels of RNA polymerase II, ensuring co-directional replication of the most highly transcribed genes. Further, we demonstrate that dormant replication origin firing represents the global activation of pre-existing origins. We also show that DNA replication naturally terminates at the polyadenylation site of transcribed genes. During replication stress, termination is redistributed to gene bodies, generating a global reorientation of replication relative to transcription. Our analysis provides a unified model for the coupling of transcription with replication initiation and termination in human cells.

molecular biology↗

bioRxiv2018

Integrated RNA-seq and sRNA-seq revealed differences in transcriptome between susceptible and resistant tomato responding to Fusarium oxysporum

Tomato wilt disease caused by Fusarium oxysporum f. sp. lycopersici (FOL) is a worldwide destructive disease of tomato. As exploring gene expression and function approaches constitute an initial point for investigating pathogen-host interaction, we performed RNA-seq and sRNA-seq analysis to unravel regulated genes and miRNAs in tomato infected by FOL. Differentially expressed (DE) protein coding gene and miRNA gene profiles upon inoculation with FOL were presented at twenty-four hours post-inoculation including four treatments. Total of more than 182.6 million and 132.2 million high quality clean reads were obtained by RNA-seq and sRNA-seq, respectively. A large overlap was found in DE mRNAs between susceptible cultivar Moneymaker and resistant cultivar Motelle. All Gene Ontology terms were mainly classified into catalytic activity, metabolic process and binding. Combining with qRT-PCR, five disease resistance genes, Solyc01g095630, Solyc03g059080, Solyc00g174340, Solyc11g071750 and Solyc05g050350, were verified to involved in the disease resistance in the resistant cultivar Motelle treated with FOL. Northern blot analysis further confirmed the results from sRNA-Seq and demonstrated that several miRNAs including Sly-miR477-5p, sly-miR167a, novel_mir_675, novel_mir_504 and novel_mir_762 conferred FOL infection. Our data resulted that pathogen resistant genes/miRNAs may play a critical role with the benefit of a coordinated machinery in prompting the response in prompting FOL response in tomato, which offered us with a future direction and surely help in generating models of mediated resistance responses with assessment of genomic gene expression patterns.

molecular biology↗

bioRxiv2018

Molecular analysis of long non-coding RNA GAS5 and microRNA-34a expression signature in common solid tumors: A pilot study

Accumulating evidence indicates that non-coding RNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs) are aberrantly expressed in cancer, providing promising biomarkers for diagnosis, prognosis and/or therapeutic targets. We aimed in the current work to quantify the expression profile of miR-34a and one of its bioinformatically selected partner lncRNA growth arrest-specific 5 (GAS5) in a sample of Egyptian cancer patients, including three prevalent types of cancer in our region; renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and glioblastoma (GB) as well as to correlate these expression profiles with the available clinicopathological data in an attempt to clarify their roles in cancer. Quantitative real-time polymerase chain reaction analysis was applied. Different bioinformatics databases were searched to confirm the potential miRNAs-lncRNA interactions of the selected ncRNAs in cancer pathogenesis. GAS5 was significantly under-expressed in the three types of cancer. However, levels of miR-34a greatly varied according to the tumor type; it displayed an increased expression in RCC [4.05 (1.003-22.69), p <0.001] and a decreased expression in GB [0.35 (0.04-0.95), p <0.001]. A weak negative correlation was observed between levels of GAS5 and miR-34a in GB [r = -0.39, p =0.006]. Univariate analyses revealed a correlation of GAS5 downregulation with poor disease-free survival (r = 0.31, p =0.018) and overall survival (r = 0.28, p =0.029) in RCC but not in GB, and a marginal significance correlation with a higher number of lesions in HCC. Hierarchical clustering analysis showed RCC patients among others, could be clustered by GAS5 and miR-34a co-expression profile. Our results confirm the tumor suppressor role of GAS5 in cancer and suggest its potential applicability to be a predictor of bad outcomes with other conventional markers for various types of cancer. Further functional validation studies are warranted to confirm miR-34a/GAS5 interplay in cancer.

molecular biology↗

bioRxiv2018

Messenger RNAs transcribed from yeast linear cytoplasmic plasmids possess unconventional 5’ and 3’ UTRs and suggest a novel mechanism of translation

Linear plasmids with almost identical compact genetic organization have been found in the cytoplasm of yeast species from nine genera. We employed pGKL1,2 plasmids from Kluyveromyces lactis as a model to investigate the previously unstudied transcriptome of yeast cytoplasmic linear plasmids. We performed 5 and 3 RACE analysis of all the pGKL1,2 mRNAs and found them not 3 polyadenylated and containing mostly uncapped 5 poly(A) leaders that are not complementary to the plasmid DNA. The degree of 5 capping and/or 5 polyadenylation is specific to each gene and is controlled by the corresponding promoter regions. We refined the description of the pGKL1,2 promoters and found new alternative promoters of several genes. We also provide evidence that K2ORF3 encodes an mRNA cap guanine-N7-methyltransferase and that 5 capped pGKL1,2 transcripts contain N7-methylated caps. Translation of pGKL1,2 transcripts is enhanced in Ism1{Delta} and pab1{Delta} strains and is independent of eIF4E and Pab1 translation factors. We suggested a model of a primitive regulation of pGKL1,2 plasmids gene expression where degree of 5 mRNA capping, degree of 5 non-template polyadenylation and presence of negative regulators as PAB1 and Lsm1 play an important role. Our data also suggest a close relationship between linear plasmids and poxviruses.

molecular biology↗

bioRxiv2018

Replication stress induced by CCNE1 overexpression creates a dependency on XRCC2 at the replication fork

Across multiple cancer types, genome instability has been linked to aberrant over-expression of CCNE1 due to premature cell cycle entry and replication stress. Using a gain-of-function screen, we found that XRCC2 cooperates with CCNE1 in the neoplastic transformation of TP53 mutant cells. A pan-cancer analysis of TCGA data revealed a striking correlation between CCNE1 and XRCC2 expression and knockdown of XRCC2 in Cyclin E1 overexpressing cell lines is synthetic lethal. Immunopurification of XRCC2 showed that it interacts with the Minichromosome Maintenance Complex Component 7 (MCM7) protein. This interaction appears to be critical for protecting replication forks as knockdown of XRCC2 leads to a strong increase in MCM7 ubiquitination with concomitant decrease in MCM7 protein levels, and reduced replication fork speed. Importantly, Overexpression of MCM7 rescues the effect of XRCC2 knockdown. Our data describe a new dependency of Cyclin E1 overexpressing tumors on factors that stabilize the replication fork.

molecular biology↗

bioRxiv2018

Autonomous functionality of an upstream open reading frame in polycistronic mammalian mRNAs

Upstream open reading frames (uORFs) are established as cis-acting elements for eukaryotic translation of annotated ORFs (anORFs) located on the same mRNAs. Here, we identified a mammalian uORF with functions that are independent from anORF translation regulation. Bioinformatics screening using ribosome profiling data of human and mouse brains yielded 308 neurologically vital genes from which anORF and uORFs are polycistronically translated in both species. Among them, Arhgef9 contains a uORF named SPICA, which is highly conserved among vertebrates and stably translated only in specific brain regions of mice. Disruption of SPICA translation by ATG-to-TAG substitutions did not perturb translation or function of its anORF product, collybistin. SPICA-null mice displayed abnormal maternal reproductive performance and enhanced anxiety-like behavior, characteristic of ARHGEF9-associated neurological disorders. This study demonstrates that mammalian uORFs can be independent genetic units, revising the prevailing dogma of the monocistronic gene in mammals, and even eukaryotes.

molecular biology↗

bioRxiv2018

A novel histone H4 variant regulates rDNA transcription in breast cancer

Histone variants, present in various cell types and tissues, are known to exhibit different functions. For example, histone H3.3 and H2A.Z are both involved in gene expression regulation, whereas H2A.X is a specific variant that responds to DNA double-strand breaks. In this study, we characterized H4G, a novel hominidae-specific histone H4 variant. H4G expression was found in a variety of cell lines and was particularly overexpressed in the tissues of breast cancer patients. H4G was found to localize primarily to the nucleoli of the cell nucleus. This localization was controlled by the interaction of the alpha helix 3 of the histone fold motif with the histone chaperone, nucleophosphomin 1. In addition, we found that H4G nucleolar localization increased rRNA levels, protein synthesis rates, and cell cycle progression. Furthermore, micrococcal nuclease digestion of H4G-containing nucleosomes reconstituted in vitro indicated that H4G destabilizes the nucleosome, which may serve to alter nucleolar chromatin in a way that enhances rDNA transcription in breast cancer tissues.

molecular biology↗

bioRxiv2018

Transposable element insertions shape gene regulation and melanin production in a fungal pathogen

Background\n\nVariation in gene expression contributes to phenotypic diversity within species and adaptation. However, very few cases of adaptive regulatory changes have been reported and the mechanisms underlying variation in gene expression remain largely unexplored. Fungal pathogen genomes are highly plastic and harbour numerous insertions of transposable elements, which can potentially contribute to gene expression regulation. In this work we elucidated how transposable elements contribute to variation of melanin accumulation, a quantitative adaptive trait of fungal pathogens that is involved in survival under stress conditions.\n\nResults\n\nWe demonstrated that differential transcriptional regulation of the gene encoding the transcription factor Zmr1, which controls expression of the genes in the melanin biosynthetic gene cluster, is responsible for variation in melanin accumulation in the fungal plant pathogen Zymoseptoria tritici. We show that differences in melanin levels between two strains of Z. tritici are due to two levels of transcriptional regulation: 1) variation in the promoter sequence of Zmr1, and 2) an insertion of transposable elements upstream of the Zmr1 promoter. Remarkably, independent insertions of transposable elements upstream of Zmr1 occurred in 9% of Z. tritici strains from around the world and negatively regulated Zmr1 expression, contributing to melanin accumulation variation.\n\nConclusions\n\nOur studies demonstrate that different layers of transcriptional control fine-tune the synthesis of melanin. These regulatory mechanisms potentially evolved to balance the fitness costs associated with melanin production against its positive contribution to survival in stressful environments.

molecular biology↗

bioRxiv2018

Molecular dynamics simulation reveals that switchable combinations of β-sheets underlie the prion-like properties of α-synuclein amyloids.

Diversity of prion strains is one of the most mysterious traits of prions because they are mere aggregates of abnormally-folded forms of single protein species, prion protein (PrPSc), without genome. Although the strain-specific properties are hypothesized to be enciphered in the strain-specific structures of PrPSc instead of nucleotide genome, specifically what structure can code the information remains an enigma due to the incompatibility of PrPSc with structural analyses. Although the strain diversity was regarded as unique to prions, recently other disease-associated amyloids of -synuclein (Syn) or tau are also reported to have \"strains\". As detailed structures of Syn amyloid are already identified and the properties of mutant Syn associated with familial Parkinsons diseases, e.g. A53T, H50Q, and G51D, have been characterized, structure-phenotype relations of this type of amyloid could be investigated by using the Syn amyloid as a model. Here we intensively investigated the mutant Syn amyloids by molecular dynamics simulation to characterize influences of mutations on the structures of homo- or hetero-oligomer stacks of the amyloid. The simulations revealed directionality of the amyloid stack, remote effects of the mutations on distant {beta}-sheets, existence of at least two switchable interfaces/amyloid cores, and distinct effects of hetero-oligomerization depending on mutation types. Collectively, those findings implied a possible mechanism of the strain diversity of the amyloids which have multiple in-register parallel {beta}-sheets side-by-side, and support the view that their prion-like properties are inherent in the characteristic structures. We expect that the notion is also applicable to PrPSc.

molecular biology↗

bioRxiv2018

Urine proteome changes in a TNBS-induced colitis rat model

Urine is an important resource for biomarker research. Without homeostasis, urine accumulates markers of all the changes in the body. Urine proteins reflect not only renal diseases but also changes in other organs in the body. However, urine has rarely been used to reflect inflammatory bowel disease. In the present study, a trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model was used to mimic the human inflammatory bowel disease Crohns disease (CD). Urine samples from a control group (n=3), a TNBS 2-day group (n=3) and a TNBS 7-day group (n=3) were analyzed for candidate biomarker discovery by label-free and TMT-labeled proteomic quantitative methods. Seventy-seven urinary proteins were significantly changed in the colitis rats compared with that in the controls. These proteins were further validated by parallel reaction monitoring (PRM) targeted proteomic quantitative methods. Urine samples from the control group (n=8), the TNBS 2-day group (n=11) and the TNBS 7-day group (n=11) were analyzed by PRM. This led to the identification of 9 significantly differential expressed urinary proteins: CAH1, G3P, MMP-8, MANBA, NGAL, RNS1G, SLC31, S6A18, and TMM27. Based on the human protein tissue atlas, CAH1, RNS1G and SLC31 are highly enriched in the gastrointestinal tract. Among the 9 PRM-validated proteins, CAH1, MMP-8 and NGAL were previously reported as IBD-associated proteins (all exhibiting consistent trends with our observation), whereas the others are newly discovered by this study. Our results provide valuable clues for future study of urine biomarker of inflammatory bowel disease and Crohns disease.

molecular biology↗

bioRxiv2018

Diagnostic host gene signature to accurately distinguish enteric fever from other febrile diseases

Misdiagnosis of enteric fever is a major global health problem resulting in patient mismanagement, antimicrobial misuse and inaccurate disease burden estimates. Applying a machine-learning algorithm to host gene expression profiles, we identified a diagnostic signature which could accurately distinguish culture-confirmed enteric fever cases from other febrile illnesses (AUROC<95%). Applying this signature to a culture-negative suspected enteric fever cohort in Nepal identified a further 12.6% as likely true cases. Our analysis highlights the power of data-driven approaches to identify host-response patterns for the diagnosis of febrile illnesses. Expression signatures were validated using qPCR highlighting their utility as PCR-based diagnostic for use in endemic settings.

molecular biology↗

bioRxiv2018

DYRK1A regulates the recruitment of 53BP1 to the sites of DNA damage in part through interaction with RNF169

Human DYRK1A gene encoding Dual-specificity tyrosine (Y)- Regulated Kinase 1A (DYRK1A) is a dosage-dependent gene whereby either trisomy or haploinsufficiency result in developmental abnormalities. However, the function and regulation of this important protein kinase are not fully understood. Here we report proteomic analysis of DYRK1A in human cells that revealed a novel role of DYRK1A in the DNA double-strand break (DSB) repair signaling. This novel function of DYRK1A is mediated in part by its interaction with ubiquitin-binding protein RNF169 that regulates the choice between homologous recombination (HR) and non-homologous end joining (NHEJ) DSB repair. Accumulation of RNF169 at the DSB sites promotes homologous recombination (HR) by limiting the recruitment of the scaffold protein 53BP1 that promotes NHEJ by protecting the DNA ends from resection. Inducible overexpression of active, but not the kinase inactive, DYRK1A in U-2 OS cells inhibited accumulation of 53BP1 at the DSB sites in RNF169-dependent manner. Mutation of DYRK1A phosphorylation sites in RNF169 or pharmacological inhibition of DYRK1A using harmine decreased the ability of RNF169 to displace 53BP1 from radiation-induced DSB sites. In order to further investigate the role of DYRK1A in regulation of DNA repair, we used CRISPR-Cas9 mediated knockout of DYRK1A in human and mouse cells. Interestingly, knockout of DYRK1A also caused a defect in 53BP1 DSB recruitment that was independent of RNF169, suggesting that dosage of DYRK1A can influence the DNA repair processes through several mechanisms. U-2 OS cells devoid of DYRK1A displayed an increased DNA repair and HR efficiency, and showed a decreased sensitivity to the PARP inhibitor olaparib when compared to control cells. Given evidence of its altered expression in human cancers, DYRK1A levels could represent a significant determinant of the DNA damaging therapy response.

molecular biology↗

bioRxiv2018

Circulating proteomic patterns in AF related left atrial remodeling indicate involvement of coagulation and complement cascade

BackgroundLeft atrial (LA) electro-anatomical remodeling and diameter increase in atrial fibrillation (AF) indicates disease progression and is associated with poor therapeutic success. Furthermore, AF leads to a hypercoagulable state, which in turn promotes the development of a substrate for AF and disease progression in the experimental setting. The aim of this study was to identify pathways associated with LA remodeling in AF patients using untargeted proteomics approach.\n\nMethodsPeripheral blood samples of 48 patients (62{+/-}10 years, 63% males, 59% persistent AF) undergoing AF catheter ablation were collected before ablation. 24 patients with left atrial low voltage areas (LVA), defined as <0.5 mV, and 24 patients without LVA were matched for age, gender and CHA2DS2-VASc score. Untargeted proteome analysis was performed using LC-ESI-Tandem mass spectrometry in a label free intensity based workflow. Significantly different abundant proteins were identified and used for pathway analysis and protein-protein interaction analysis.\n\nResultsAnalysis covered 280 non-redundant circulating plasma proteins. The presence of LVA correlated with 30 differentially abundant proteins of coagulation and complement cascade (q<0.05).\n\nConclusionsThis pilot proteomic study identified plasma protein candidates associated with electro-anatomical remodeling in AF and pointed towards an imbalance in coagulation and complement pathway, tissue remodeling and inflammation

molecular biology↗

bioRxiv2018

The RNA demethylase FTO targets m6Am in snRNA to establish distinct methyl isoforms that influence splicing

Small nuclear RNAs (snRNAs) are core spliceosome components and mediate pre-mRNA splicing. During their biogenesis, snRNAs acquire several constitutive nucleotide modifications. Here we show that snRNAs also contain a regulated and reversible nucleotide modification causing them to exist as two different methyl isoforms, m1 and m2, reflecting the methylation state of the adenosine adjacent to the snRNA cap. We find that snRNA biogenesis involves the formation of an initial m1-isoform with a single-methylated adenosine (2-O-methyladenosine, Am), which is then converted to a dimethylated m2-isoform (N6,2-O-dimethyladenosine, m6Am). The relative m1- and m2-isoform levels are determined by the RNA demethylase FTO, which selectively demethylates the m2-isoform. We show FTO is inhibited by endogenous metabolites, resulting in increased m2-snRNA levels. Furthermore, cells that exhibit high m2-snRNA levels show altered patterns of alternative splicing. Together, these data reveal that FTO has a central role in snRNA biogenesis and controls a previously unknown step of snRNA processing involving reversible methylation, thereby providing a potential link between reversible RNA modifications and mRNA splicing.

molecular biology↗

bioRxiv2018

Non-coding AUG circRNAs constitute an abundant and conserved subclass of circles

Circular RNAs (circRNAs) are a subset of noncoding RNAs (ncRNAs) previously considered as products of missplicing. Now, circRNAs are considered functional molecules, although to date, only few functions have been experimentally validated, and therefore the vast majority of circRNAs are without known relevance. Here, based on RNA sequencing from the ENCODE consortium, we identify and characterize a subset of circRNAs, coined AUG circRNAs, defined by spanning the canonical translational start site in the protein-coding host genes. AUG circRNAs are more abundantly expressed and conserved than other groups of circRNAs, and they display an Alu-independent mechanism of biogenesis. The AUG circRNAs contain part of bona fide ORF, and in the recent years, several studies have reported cases of circRNA translation. However, using thorough cross-species analysis, extensive ribosome profiling analyses and experimental data on a selected panel of AUG circRNAs, we observe no indications of translation of AUG circRNAs or any other circRNAs. Our data provide a comprehensive classification of circRNAs and, collectively, the analyses suggest that the AUG circRNAs constitute an abundant subclass of circRNAs produced independently of primate-specific Alu elements. Moreover, AUG circRNAs exhibit high cross-species conservation and are therefore likely to be functionally relevant.

molecular biology↗

bioRxiv2018

Biophysical Principles of Lineage Factor PU.1 Binding Revealed by NextPBMs

Determining the biophysical principles that shape transcription factor (TF) binding in a cell-specific manner is key to quantitative models of gene expression. High-throughput (HT) in vitro methods measuring protein-DNA binding are invaluable for relating TF binding affinity to genome-wide binding; however, the impact of cell-specific post-translational modifications (PTMs) and cofactors are not routinely assessed. To address these limitations, we describe a new HT approach, called nextPBMs (nuclear extract protein-binding microarrays), to characterize TF binding that accounts for PTMs and endogenous cofactors. We use nextPBMs to examine the DNA binding of the lineage factor PU.1/Spi1 and IRF8 in human monocytes. We identify two binding modes for PU.1 in monocytes - autonomous binding unaffected by PTMs and cooperative binding with IRF8, and identify a single cooperative mode for IRF8. We characterize the DNA binding of PU.1:IRF8 complexes, and show how nextPBMs can be used to discover cell-specific cofactors and characterize TF cooperativity at single-nucleotide resolution. We show that chromatin state and cofactors both influence the affinity requirements for PU.1 binding sites. Furthermore, we find that the influences of cooperative (IRF8) and collaborative (C/EBP) cofactors on PU.1-binding-site affinity are independent and additive.

molecular biology↗

bioRxiv2018

Olive mild mosaic virus coat protein and p6 are suppressors of RNA silencing and their silencing confers resistance against OMMV

RNA silencing is an important defense mechanism in plants, yet several plant viruses encode proteins that suppress it. Here the genome of Olive mild mosaic virus (OMMV) was screened for silencing suppressors using a green fluorescent based transient suppression assay. The full OMMV cDNA and 5 different OMMV open reading frames (ORFs) were cloned into Gateway binary destination vector pK7WG2, transformed into Agrobacterium tumefaciens C58C1 and agroinfiltrated into Nicotiana benthamiana 16C plants. Among all ORFs tested, CP and p6 showed suppressor activity, with CP showing a significant higher activity when compared to p6, yet lower than that of the full OMMV. This suggests that OMMV silencing suppression results from a complementary action of both CP and p6.\n\nSuch discovery led to the use of those viral suppressors in the development of OMMV resistant plants through pathogen-derived resistance (PDR) based on RNA silencing. Two hairpin constructs targeting each suppressor were agroinfiltrated in N. benthamiana plants which were then inoculated with OMMV RNA. When silencing of both suppressors was achieved, a highly significant reduction in viral accumulation and symptom attenuation was observed as compared to that seen when each construct was used alone, and to the respective controls, thus showing clear effectiveness against OMMV infection. Data here obtained indicate that the use of both OMMV viral suppressors as transgenes is a very efficient and promising approach to obtain plants resistant to OMMV.\n\nImportanceOMMV silencing suppressors were determined. Among all ORFs tested, CP and p6 showed suppressor activity, with CP showing a significant higher activity when compared to p6, yet lower than that of the full OMMV, suggesting a complementary action of both CP and p6 in silencing suppression.\n\nThis is the first time that a silencing suppressor was found in a necrovirus and that two independent proteins act as silencing suppressors in a member of the Tombusviridae family.\n\nWhen silencing of both suppressors was achieved, a highly significant reduction in viral accumulation and symptom attenuation was observed as compared to that seen when each was used alone, thus showing clear effectiveness against OMMV infection. A high percentage of resistant plants was obtained (60%), indicating that the use of both OMMV viral suppressors as transgenes is a very efficient and promising approach to obtain plants resistant to OMMV.

molecular biology↗

bioRxiv2018

Alternative super-enhancers result in similar gene expression in different tissues

Super-enhancers (SEs) are clusters of highly active enhancers, regulating cell type-specific and disease-related genes, including oncogenes1-3. The individual regulatory regions within SEs might be simultaneously bound by different transcription factors (TFs) and co-regulators such as P300, BRD4 and Mediator, which together establish a chromatin environment conducting to effective gene induction4-6. While cells with distinct TF profiles can have different functions, an unanswered question is how different cells control overlapping genetic programmes. Here, we show that the construction of oestrogen receptor alpha (ER)-driven SEs is tissue specific, and both the collaborating TFs and the active SE components are largely differing between human breast cancer-derived MCF-7 and endometrial cancer-derived Ishikawa cells; nonetheless, SEs common to both cell types have similar transcriptional outputs. In the MCF-7 cell line, ER-dominated SEs are also driven by the well-known FoxA1 and AP2{gamma} TFs, as described previously7, whereas in Ishikawa cells, FoxM1, TCF12 and TEAD4 are as important as ER for SE formation. Our results show that SEs can be constructed in several ways, but the overall activity of common SEs is the same between cells with a common master regulator. These findings may reshape our current understanding of how these regulatory units can fine-tune cell functions. From a broader perspective, we show that systems assembled from different components can perform similar tasks if a common functional trigger drives their assembly.

molecular biology↗