4D nucleome equation predicts gene expression controlled by long-range enhancer-promoter interaction
Recent experimental evidence strongly supports that three-dimensional (3D) long-range enhancer-promoter (E-P) interactions have important influences on gene-expression dynamics, but it is unclear how the interaction information is translated into gene expression over time (4D). To address this quest...
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Published in | PLoS computational biology Vol. 19; no. 12; p. e1011722 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
18.12.2023
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | Recent experimental evidence strongly supports that three-dimensional (3D) long-range enhancer-promoter (E-P) interactions have important influences on gene-expression dynamics, but it is unclear how the interaction information is translated into gene expression over time (4D). To address this question, we developed a general theoretical framework (named as a 4D nucleome equation), which integrates E-P interactions on chromatin and biochemical reactions of gene transcription. With this equation, we first present the distribution of mRNA counts as a function of the E-P genomic distance and then reveal a power-law scaling of the expression level in this distance. Interestingly, we find that long-range E-P interactions can induce bimodal and trimodal mRNA distributions. The 4D nucleome equation also allows for model selection and parameter inference. When this equation is applied to the mouse embryonic stem cell smRNA-FISH data and the E-P genomic-distance data, the predicted E-P contact probability and mRNA distribution are in good agreement with experimental results. Further statistical inference indicates that the E-P interactions prefer to modulate the mRNA level by controlling promoter activation and transcription initiation rates. Our model and results provide quantitative insights into both spatiotemporal gene-expression determinants (i.e., long-range E-P interactions) and cellular fates during development. |
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Bibliography: | new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors have declared that no competing interests exist. |
ISSN: | 1553-7358 1553-734X 1553-7358 |
DOI: | 10.1371/journal.pcbi.1011722 |