Dynamical gene regulatory networks are tuned by transcriptional autoregulation with microRNA feedback
AuthorsMinchington, Thomas G.
Griffiths-Jones, Sam; email: email@example.com
Papalopulu, Nancy; email: firstname.lastname@example.org
MetadataShow full item record
AbstractAbstract: 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.
CitationScientific Reports, volume 10, issue 1, page 12960
PublisherNature Publishing Group UK
DescriptionFrom Springer Nature via Jisc Publications Router
History: received 2020-03-05, accepted 2020-07-06, registration 2020-07-21, pub-electronic 2020-07-31, online 2020-07-31, collection 2020-12
Publication status: Published
Funder: Wellcome Trust; doi: http://dx.doi.org/10.13039/100004440; Grant(s): 110566/Z/15/Z, 090868/Z/09/Z
Funder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/M011275/1