Bursty gene expression and mRNA decay pathways orchestrate B cell activation

爆发性基因表达和 mRNA 衰减途径调控 B 细胞活化

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作者:Yi Zhou, Cornelis Murre

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 E2A and E2-2 gene expression is regulated. We found that E2A and E2-2 mRNA abundance concomitantly increased in activated B cells. The increase in E2A and E2-2 mRNA abundance correlated with increased cell growth. Elevated E2A and E2-2 mRNA abundance was instructed by increased transcriptional bursting frequencies and elevated E2A and E2-2 mRNA half-lives. The increase in E2A and E2-2 bursting frequencies often occurred at shared interchromosomal transcriptional hubs. We suggest that in naïve B cells low E2A and E2-2 bursting frequencies and high E2A and E2-2 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.

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