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First published online January 21, 2009

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Return-to-template for transcription?

Gene regulation in the average cell population can appear to be deterministic but, at the single-cell level, transcription is a probabilistic process. To address this disparity between the deterministic and probabilistic models of gene regulation, Gordon L. Hager and colleagues (p. 345) perform a single-cell analysis of interactions between the glucocorticoid receptor (GR) and coregulators with a target promoter, and analyse the resulting transcriptional output. The researchers find that many different combinations of GR-cofactor-promoter complexes are produced via a probabilistic mechanism at the single-cell level. The heterogeneity of gene expression within the cell population is regulated by the variant promoter states, which influence transcription in individual cells. Importantly, the authors' statistical analysis indicates that the multiple steps of this process are partially independent and differ between individual regulators. Time-dependent transcriptional activity is observed in many endogenous genes, which appears to be deterministic in averaged cell populations; this deterministic behaviour is produced by time-dependent changes in the probabilistic interactions of the GR and cofactors with the promoter. Thus, argue the authors, probabilistic combinations of transcription-factor interactions produce heterogeneous gene expression at the single-cell level, which then appears as deterministic behaviour when observed at the population level.

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Combinatorial probabilistic chromatin interactions produce transcriptional heterogeneity

Ty C. Voss, R. Louis Schiltz, Myong-Hee Sung, Thomas A. Johnson, Sam John, and Gordon L. Hager
JCS 2009 122: 345-356. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?