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Stochastic model for IL-4 expression dynamics
From Q-bio
Luca Mariani, Max Löhning, and Thomas Höfer
- Abstract
- The alleles of the Interleukin-4 (IL-4) gene are expressed in a highly stochastic manner in T cells. We studied the kinetics of IL-4 induction at different stages of T-memory cell development, linking stochastic modeling to single cell expression data. To explain the observed fluctuations in IL-4 protein, we had to introduce a multi-step process of gene induction, with the opening of chromatin structure and the assembly of the transcription initiation complex as sequential random events. Under reasonable assumptions on the kinetic parameters, the model is able to explain the experimental data and predicts: (1) IL-4 expression is preceded by slow, transient chromatin opening; (2) chromatin accessibility increases as T-memory cells mature; (3) mRNA is transcribed in infrequent bursts during a limited time window of transcription factor availability.
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