Spatial clustering and common regulatory elements correlate with coordinated gene expression
AffiliationUniv Arizona, Dept Mol & Cellular Biol
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationZhang J, Chen H, Li R, Taft DA, Yao G, Bai F, et al. (2019) Spatial clustering and common regulatory elements correlate with coordinated gene expression. PLoS Comput Biol 15(3): e1006786. https://doi.org/10.1371/journal.pcbi.1006786
JournalPLOS COMPUTATIONAL BIOLOGY
Rights© 2019 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractMany cellular responses to surrounding cues require temporally concerted transcriptional regulation of multiple genes. In prokaryotic cells, a single-input-module motif with one transcription factor regulating multiple target genes can generate coordinated gene expression. In eukaryotic cells, transcriptional activity of a gene is affected by not only transcription factors but also the epigenetic modifications and three-dimensional chromosome structure of the gene. To examine how local gene environment and transcription factor regulation are coupled, we performed a combined analysis of time-course RNA-seq data of TGF- treated MCF10A cells and related epigenomic and Hi-C data. Using Dynamic Regulatory Events Miner (DREM), we clustered differentially expressed genes based on gene expression profiles and associated transcription factors. Genes in each class have similar temporal gene expression patterns and share common transcription factors. Next, we defined a set of linear and radial distribution functions, as used in statistical physics, to measure the distributions of genes within a class both spatially and linearly along the genomic sequence. Remarkably, genes within the same class despite sometimes being separated by tens of million bases (Mb) along genomic sequence show a significantly higher tendency to be spatially close despite sometimes being separated by tens of Mb along the genomic sequence than those belonging to different classes do. Analyses extended to the process of mouse nervous system development arrived at similar conclusions. Future studies will be able to test whether this spatial organization of chromosomes contributes to concerted gene expression. Author summary Cellular responses to environmental stimulation are often accompanied by changes in gene expression patterns. Genes are linearly arranged along chromosomal DNA, which folds into a three-dimensional structure. The chromosome structure affects gene expression activities and is regulated by multiple events such as histone modifications and DNA binding of transcription factors. A basic question is how these mechanisms work together to regulate gene expression. In this study, we analyzed temporal gene expression patterns in the context of chromosome structure both in a human cell line under TGF- treatment and during mouse nervous system development. In both cases, we observed that genes regulated by common transcription factors have an enhanced tendency to be spatially close. Our analysis suggests that spatial co-localization of genes may facilitate the concerted gene expression.
NoteOpen access journal
VersionFinal published version
SponsorsNational Science Foundation [DMS-1462049, DMS-1463137]; Charles E. Kaufman Fund of the Pittsburgh Foundation [KA2018-98550]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK119232]; National Key Research and Development Program of China [2016YFC0900102]; National Science and Technology Major Project of China [2018ZX10302205]; National Natural Science Foundation of China [31722003, 31770925]
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