Transcription pause and elongation regulators mediate somatic hypermutation.
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NELF, MLLT1, MLLT3, and INT-PP2A are essential for somatic hypermutation by facilitating stalled PolII and AID targeting in B cells.
- Why it matters: Understanding how AID is recruited to specific gene regions during SHM is crucial for comprehending antibody diversity and preventing off-target mutations that can lead to lymphomas.
- What they did: The study examined the roles of transcription regulators by demonstrating that NELF, MLLT1, MLLT3, and INT-PP2A are necessary for SHM, with NELF associating with PolII and aiding AID recruitment in gene bodies.
- The result: Disruption of these factors impairs AID activity despite normal chromatin binding, revealing their key function in creating stalled PolII substrates that enable targeted mutation during antibody maturation.