Beyond the packaging of genome into nucleosomes, chromosomes are further organized into high-order structures in the 3D nuclear space. In recent years, imaging and 3C-based measurements revealed intricate chromosome folding patterns with extensive long-distance chromosomal interactions. There are a few proposed models of how these interactions may regulate gene expression, including enhancer-promoter looping, multi-gene clusters, and transcription factory. However, we have limited understanding of the molecular basis for these phenomena. The long-term goal here is to understand the formation mechanism of these high-order structures and elucidate their functions in gene regulation. Budding yeast was traditionally considered not to be a good model of long-distance gene regulation. However, my lab and several others recently found evidence that 3D conformation contribute to gene regulation in yeast. More specifically, we found long-distance gene regulation with two different genetic constructs. In the first case, we showed that two allelic GAL1 reporters (one with wild-type GAL1 promoter and the other mutated) physically interact upon galactose induction, and the wild-type promoter facilitates the firing of the mutant promoter. In the second case, we found that the MET3pr-GFP reporter clusters with other co-regulated MET genes, and the clustering is correlated with higher transcriptional activity. We are currently investigating the molecular mechanism of the hyper-activity of these MET clusters. Overall, these novel findings opened the opportunity of using the powerful yeast genetics to investigate the 3D genome function.

Related publication:

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    Zou F, Du MY, Chen HY, & Bai L (2019)
    Mol. Cell. Biol, pii: MCB.00146-19.
  • 3D clustering of co-regulated genes and its effect on gene expression.
    Du MY & Bai L (2017)
    Current Genetics, doi: 10.1007/s00294-017-0712-9.
  • Three distinct mechanisms of long-distance modulation of gene expression in yeast.
    Du MY, Zhang Q, & Bai L (2017)
    PLOS Genetics, 13(4):e1006736.
  • Inter-allelic interaction and gene regulation in budding yeast.
    Zhang DY & Bai L (2016)
    PNAS, 113:4428-33.