Transcriptional heterogeneity arising from a signal transduction-transcription factor network

Prof. Mariko Okada
Laboratory for Cell Systems, Institute for Protein Research, Osaka University 

Abstract:
Cells make individual fate decisions through dynamic gene regulatory networks. In this talk, I will present our recent work in which heterogeneity in gene expression, the so-called non-genetic heterogeneity, is viewed as an integrated output of a signaling-transcription factor network. In B cells, the antigen-activated NF-kB signaling pathway leads to all or none activation of the NF-kB nuclear translocation, followed by similar (all or none) or different (graded) expression patterns of its target genes. In addition to the result that NF-kB foci formation was inhibited by LLPS (liquid-liquid phase separation) inhibitors, the co-occurrence of chromatin openings in the enhancer region contributes to cell-to-cell gene expression heterogeneity after cell stimulation, suggesting that the higher-order structure of DNA may contribute to gene expression heterogeneity. study shows that even when extracellular signaling is uniformly regulated, the noise in gene expression is strongly controlled by differences in the kinetics of nuclear translocation of NF-kB and the dynamics of chromatin opening.