Transcription factor YY1 can control AID-mediated mutagenesis in mice

Kristina Zaprazna, Arindam Basu, Nikola Tom, Vibha Jha, Suchita Hodawadekar, Lenka Radova, Jitka Malcikova, Boris Tichy, Sarka Pospisilova, Michael L. Atchison

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease. We previously showed that transcription factor YY1 can regulate the level of AID in the nucleus and Ig CSR. Therefore, we hypothesized that conditional knock-out of YY1 would lead to reduction in AID localization at the Ig locus, and reduced AID-mediated mutations. Using mice that overexpress AID (IgκAID yy1f/f) or that express normal AID levels (yy1f/f), we found that conditional knock-out of YY1 results in reduced AID nuclear levels, reduced localization of AID to the Sμ switch region, and reduced AID-mediated mutations. We find that the mechanism of YY1 control of AID nuclear accumulation is likely due to YY1-AID physical interaction which blocks AID ubiquitination.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalEuropean Journal of Immunology
Volume48
Issue number2
DOIs
StatePublished - Feb 1 2018

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Zaprazna, K., Basu, A., Tom, N., Jha, V., Hodawadekar, S., Radova, L., Malcikova, J., Tichy, B., Pospisilova, S., & Atchison, M. L. (2018). Transcription factor YY1 can control AID-mediated mutagenesis in mice. European Journal of Immunology, 48(2), 273-282. https://doi.org/10.1002/eji.201747065