Transcription elongation factor ELOF1 is required for efficient somatic hypermutation and class switch recombination

Somatic hypermutation (SHM) and class switch recombination (CSR) diversify immunoglobulin (Ig) genes and are initiated by the activation induced deaminase (AID), a single-stranded DNA cytidine deaminase that is thought to engage its substrate in the context of RNA polymerase II (RNAPII) transcription. Through a loss of function genetic screen, we identified numerous potential factors involved in SHM including ELOF1, a component of the RNAPII elongation complex that has been shown to function in DNA repair and transcription elongation. Loss of ELOF1 strongly compromises SHM, CSR, and AID targeting and alters RNAPII transcription by reducing RNAPII pausing downstream of transcription start sites and levels of serine 5 but not serine 2 phosphorylated RNAPII throughout transcribed genes. ELOF1 must bind to RNAPII to be a proximity partner for AID and to function in SHM and CSR. We propose that ELOF1 helps create the appropriate stalled RNAPII substrate on which AID acts.