Many 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-\b{eta} 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.Comment: 30 pages, 9 figures, accepted in PLoS Computational Biolog