PMID- 30822341 OWN - NLM STAT- MEDLINE VI - 15 IP - 3 TI - Spatial clustering and common regulatory elements correlate with coordinated gene expression. PG - e1006786 LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Plos Comput Biol JT - PLoS computational biology JID - 101238922 IS - 1553-7358 (Electronic) LID - 10.1371/journal.pcbi.1006786 [doi] FAU - Zhang, Jingyu AU - Zhang J AUID- ORCID: 0000-0001-6668-2815 AD - Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China. AD - Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America. FAU - Chen, Hengyu AU - Chen H AD - Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China. FAU - Li, Ruoyan AU - Li R AD - Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China. FAU - Taft, David A AU - Taft DA AUID- ORCID: 0000-0001-8472-9867 AD - Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America. FAU - Yao, Guang AU - Yao G AD - Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, United States of America. FAU - Bai, Fan AU - Bai F AUID- ORCID: 0000-0001-6119-8936 AD - Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China. FAU - Xing, Jianhua AU - Xing J AUID- ORCID: 0000-0002-3700-8765 AD - Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States of America. AD - UPMC-Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States of America. IS - 1553-734X (Linking) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Animals MH - Cell Differentiation/drug effects MH - Cell Line MH - Cluster Analysis MH - Embryonic Development MH - *Gene Expression Profiling MH - Gene-Environment Interaction MH - Humans MH - Mice MH - *Regulatory Sequences, Nucleic Acid MH - Sequence Analysis, RNA MH - Signal Transduction/drug effects MH - Transforming Growth Factor beta/pharmacology PMC - PMC6415868 DCOM- 20190429 LR - 20200309 DP - 201903 DEP - 20190301 AB - 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-β 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.