Bursty gene expression and mRNA decay pathways orchestrate B cell activation.

Zhou, Yi; Murre, Cornelis · Sci Adv · 2021

basic_science · Level V

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Abstract

It is well established that the helix-loop-helix proteins, E2A and E2-2, promote B cell activation. Here, we examined how during the course of B cell activation <i>E2A</i> and <i>E2-2</i> gene expression is regulated. We found that <i>E2A</i> and <i>E2-2</i> mRNA abundance concomitantly increased in activated B cells. The increase in <i>E2A</i> and <i>E2-2</i> mRNA abundance correlated with increased cell growth. Elevated <i>E2A</i> and <i>E2-2</i> mRNA abundance was instructed by increased transcriptional bursting frequencies and elevated <i>E2A</i> and <i>E2-2</i> mRNA half-lives. The increase in <i>E2A</i> and <i>E2-2</i> bursting frequencies often occurred at shared interchromosomal transcriptional hubs. We suggest that in naïve B cells low <i>E2A</i> and <i>E2-2</i> bursting frequencies and high <i>E2A</i> and <i>E2-2</i> mRNA decay rates instruct noisy gene expression that allows a clonal and swift response to invading pathogens whereas in activated B cells increased transcriptional bursting and low mRNA decay rates dictate an activated B lineage gene program.