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 ambient DNA condition of the gene, characterized by epigenetic modifications and the three-dimensional chromosome structure. To examine how the local gene environment and transcription factor regulation are coupled, we performed a combined analysis of time-course RNA-seq data of TGF-β treated MCF10A cells and related epigenome and Hi-C data. Using the 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 pattern and share common upstream transcription factors. Next we defined a set of linear and radial distribution functions as used in statistical physics to measure distributions of the genes within a class both along the genomic sequence and spatially. Remarkably, genes within the same class show significantly enhanced tendency to be spatially close despite sometimes being separated by tens of Mb along the genomic sequence, compared to those belonging to different classes. Analysis extended to the mouse nervous system development process leads to similar conclusions. Future studies can test whether this spatial chromosome organization contributes to concerted gene expression.
The paper site is here, and a news release in the departmental site.