Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Dynamical gene regulatory networks are tuned by transcriptional autoregulation with microRNA feedback.
Minchington TG
,
Griffiths-Jones S
,
Papalopulu N
.
???displayArticle.abstract???
Concepts from dynamical systems theory, including multi-stability, oscillations, robustness and stochasticity, are critical for understanding gene regulation during cell fate decisions, inflammation and stem cell heterogeneity. However, the prevalence of the structures within gene networks that drive these dynamical behaviours, such as autoregulation or feedback by microRNAs, is unknown. We integrate transcription factor binding site (TFBS) and microRNA target data to generate a gene interaction network across 28 human tissues. This network was analysed for motifs capable of driving dynamical gene expression, including oscillations. Identified autoregulatory motifs involve 56% of transcription factors (TFs) studied. TFs that autoregulate have more interactions with microRNAs than non-autoregulatory genes and 89% of autoregulatory TFs were found in dual feedback motifs with a microRNA. Both autoregulatory and dual feedback motifs were enriched in the network. TFs that autoregulate were highly conserved between tissues. Dual feedback motifs with microRNAs were also conserved between tissues, but less so, and TFs regulate different combinations of microRNAs in a tissue-dependent manner. The study of these motifs highlights ever more genes that have complex regulatory dynamics. These data provide a resource for the identification of TFs which regulate the dynamical properties of human gene expression.
Aibar,
SCENIC: single-cell regulatory network inference and clustering.
2017, Pubmed
Aibar,
SCENIC: single-cell regulatory network inference and clustering.
2017,
Pubmed
Alon,
Network motifs: theory and experimental approaches.
2007,
Pubmed
Ambros,
A uniform system for microRNA annotation.
2003,
Pubmed
Atkinson,
Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli.
2003,
Pubmed
Barkai,
Circadian clocks limited by noise.
2000,
Pubmed
Bartel,
MicroRNAs: target recognition and regulatory functions.
2009,
Pubmed
Baskerville,
Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes.
2005,
Pubmed
Batchelor,
Stimulus-dependent dynamics of p53 in single cells.
2011,
Pubmed
Batchelor,
Recurrent initiation: a mechanism for triggering p53 pulses in response to DNA damage.
2008,
Pubmed
Becskei,
Engineering stability in gene networks by autoregulation.
2000,
Pubmed
Becskei,
Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion.
2001,
Pubmed
Bessho,
Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock.
2003,
Pubmed
Bonev,
MicroRNA-9 Modulates Hes1 ultradian oscillations by forming a double-negative feedback loop.
2012,
Pubmed
,
Xenbase
Borchert,
RNA polymerase III transcribes human microRNAs.
2006,
Pubmed
Boukouvalas,
BGP: identifying gene-specific branching dynamics from single-cell data with a branching Gaussian process.
2018,
Pubmed
Bratsun,
Delay-induced stochastic oscillations in gene regulation.
2005,
Pubmed
Chen,
Mechanisms of deadenylation-dependent decay.
2011,
Pubmed
Chou,
miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions.
2018,
Pubmed
Chèneby,
ReMap 2018: an updated atlas of regulatory regions from an integrative analysis of DNA-binding ChIP-seq experiments.
2018,
Pubmed
Crews,
Transcriptional autoregulation in development.
2009,
Pubmed
ENCODE Project Consortium,
An integrated encyclopedia of DNA elements in the human genome.
2012,
Pubmed
ENCODE Project Consortium,
A user's guide to the encyclopedia of DNA elements (ENCODE).
2011,
Pubmed
Edgar,
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.
2002,
Pubmed
Elowitz,
A synthetic oscillatory network of transcriptional regulators.
2000,
Pubmed
Gennarino,
Identification of microRNA-regulated gene networks by expression analysis of target genes.
2012,
Pubmed
Goodfellow,
microRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states.
2014,
Pubmed
,
Xenbase
Goodwin,
Oscillatory behavior in enzymatic control processes.
1965,
Pubmed
Graf,
Heterogeneity of embryonic and adult stem cells.
2008,
Pubmed
Griffon,
Integrative analysis of public ChIP-seq experiments reveals a complex multi-cell regulatory landscape.
2015,
Pubmed
Guo,
Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq.
2019,
Pubmed
Ha,
Regulation of microRNA biogenesis.
2014,
Pubmed
Hafner,
The multiple mechanisms that regulate p53 activity and cell fate.
2019,
Pubmed
Hatakeyama,
Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation.
2004,
Pubmed
Hirata,
Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop.
2002,
Pubmed
Huang,
Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective.
2009,
Pubmed
Issler,
MicroRNA-16 feedback loop with p53 and Wip1 can regulate cell fate determination between apoptosis and senescence in DNA damage response.
2017,
Pubmed
Kiełbasa,
Transcriptional autoregulatory loops are highly conserved in vertebrate evolution.
2008,
Pubmed
Kim,
MicroRNA biogenesis: coordinated cropping and dicing.
2005,
Pubmed
Kobayashi,
Hes1 oscillation: making variable choices for stem cell differentiation.
2010,
Pubmed
Kozomara,
miRBase: integrating microRNA annotation and deep-sequencing data.
2011,
Pubmed
Lai,
Understanding microRNA-mediated gene regulatory networks through mathematical modelling.
2016,
Pubmed
Lamouille,
Regulation of epithelial-mesenchymal and mesenchymal-epithelial transitions by microRNAs.
2013,
Pubmed
Lee,
MicroRNA genes are transcribed by RNA polymerase II.
2004,
Pubmed
Levine,
Functional roles of pulsing in genetic circuits.
2013,
Pubmed
Ludwig,
Distribution of miRNA expression across human tissues.
2016,
Pubmed
Maeda,
Regulatory dynamics of synthetic gene networks with positive feedback.
2006,
Pubmed
Marsico,
PROmiRNA: a new miRNA promoter recognition method uncovers the complex regulation of intronic miRNAs.
2013,
Pubmed
Maston,
Transcriptional regulatory elements in the human genome.
2006,
Pubmed
Miller,
Dynamical systems, attractors, and neural circuits.
2016,
Pubmed
Milo,
Network motifs: simple building blocks of complex networks.
2002,
Pubmed
Mitrophanov,
Positive autoregulation shapes response timing and intensity in two-component signal transduction systems.
2010,
Pubmed
Monk,
Oscillatory expression of Hes1, p53, and NF-kappaB driven by transcriptional time delays.
2003,
Pubmed
Monteys,
Structure and activity of putative intronic miRNA promoters.
2010,
Pubmed
Morlando,
Primary microRNA transcripts are processed co-transcriptionally.
2008,
Pubmed
Moss Bendtsen,
The role of mRNA and protein stability in the function of coupled positive and negative feedback systems in eukaryotic cells.
2015,
Pubmed
Neems,
Turning down the volume on transcriptional noise.
2010,
Pubmed
Nguyen,
Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes.
2013,
Pubmed
North,
A note on calculation of empirical P values from Monte Carlo procedure.
2003,
Pubmed
Novák,
Design principles of biochemical oscillators.
2008,
Pubmed
Ohtsuka,
Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain.
2001,
Pubmed
Oliveira,
Combining Results from Distinct MicroRNA Target Prediction Tools Enhances the Performance of Analyses.
2017,
Pubmed
Osella,
The role of incoherent microRNA-mediated feedforward loops in noise buffering.
2011,
Pubmed
Pomaznoy,
GOnet: a tool for interactive Gene Ontology analysis.
2018,
Pubmed
Purvis,
p53 dynamics control cell fate.
2012,
Pubmed
Quinlan,
BEDTools: a flexible suite of utilities for comparing genomic features.
2010,
Pubmed
Rosenfeld,
Negative autoregulation speeds the response times of transcription networks.
2002,
Pubmed
Shimojo,
Oscillatory control of Delta-like1 in somitogenesis and neurogenesis: A unified model for different oscillatory dynamics.
2016,
Pubmed
Sikora-Wohlfeld,
Assessing computational methods for transcription factor target gene identification based on ChIP-seq data.
2013,
Pubmed
Sonnen,
Modulation of Phase Shift between Wnt and Notch Signaling Oscillations Controls Mesoderm Segmentation.
2018,
Pubmed
Stricker,
A fast, robust and tunable synthetic gene oscillator.
2008,
Pubmed
Tan,
MicroRNA9 regulates neural stem cell differentiation by controlling Hes1 expression dynamics in the developing brain.
2012,
Pubmed
Thieffry,
From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in Escherichia coli.
1998,
Pubmed
Tian,
Coupled reversible and irreversible bistable switches underlying TGFβ-induced epithelial to mesenchymal transition.
2013,
Pubmed
Tsang,
MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals.
2007,
Pubmed
Wang,
Factorbook.org: a Wiki-based database for transcription factor-binding data generated by the ENCODE consortium.
2013,
Pubmed
Yates,
Ensembl 2016.
2016,
Pubmed
