Spatial clustering and common regulatory elements correlate with coordinated gene expression

Jingyu Zhang, Hengyu Chen, Ruoyan Li, David A. Taft, Guang Yao, Fan Bai, Jianhua Xing

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e1006786
JournalPLoS computational biology
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Spatial Clustering
Gene expression
Correlate
Gene Expression
gene expression
Cluster Analysis
Genes
Gene
Transcription factors
gene
Transcription Factor
Transcription Factors
transcription factors
genes
Genomics
genomics
Chromosomes
Epigenomics
epigenetics
Chromosome

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this

Spatial clustering and common regulatory elements correlate with coordinated gene expression. / Zhang, Jingyu; Chen, Hengyu; Li, Ruoyan; Taft, David A.; Yao, Guang; Bai, Fan; Xing, Jianhua.

In: PLoS computational biology, Vol. 15, No. 3, 01.03.2019, p. e1006786.

Research output: Contribution to journalArticle

Zhang, Jingyu ; Chen, Hengyu ; Li, Ruoyan ; Taft, David A. ; Yao, Guang ; Bai, Fan ; Xing, Jianhua. / Spatial clustering and common regulatory elements correlate with coordinated gene expression. In: PLoS computational biology. 2019 ; Vol. 15, No. 3. pp. e1006786.
@article{564c1011b13642c48ab0b6b7d8776ce0,
title = "Spatial clustering and common regulatory elements correlate with coordinated gene expression",
abstract = "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.",
author = "Jingyu Zhang and Hengyu Chen and Ruoyan Li and Taft, {David A.} and Guang Yao and Fan Bai and Jianhua Xing",
year = "2019",
month = "3",
day = "1",
doi = "10.1371/journal.pcbi.1006786",
language = "English (US)",
volume = "15",
pages = "e1006786",
journal = "PLoS Computational Biology",
issn = "1553-734X",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Spatial clustering and common regulatory elements correlate with coordinated gene expression

AU - Zhang, Jingyu

AU - Chen, Hengyu

AU - Li, Ruoyan

AU - Taft, David A.

AU - Yao, Guang

AU - Bai, Fan

AU - Xing, Jianhua

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85062882169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062882169&partnerID=8YFLogxK

U2 - 10.1371/journal.pcbi.1006786

DO - 10.1371/journal.pcbi.1006786

M3 - Article

C2 - 30822341

AN - SCOPUS:85062882169

VL - 15

SP - e1006786

JO - PLoS Computational Biology

JF - PLoS Computational Biology

SN - 1553-734X

IS - 3

ER -