Dataset Information


Histone methyltransferase MMSET promotes AID-mediated DNA breaks at the donor switch region during class switch recombination.

ABSTRACT: In B cells, Ig class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID), the activity of which leads to DNA double-strand breaks (DSBs) within IgH switch (S) regions. Preferential targeting of AID-mediated DSBs to S sequences is critical for allowing diversification of antibody functions, while minimizing potential off-target oncogenic events. Here, we used gene targeted inactivation of histone methyltransferase (HMT) multiple myeloma SET domain (MMSET) in mouse B cells and the CH12F3 cell line to explore its role in CSR. We find that deletion of MMSET-II, the isoform containing the catalytic SET domain, inhibits CSR without affecting either IgH germline transcription or joining of DSBs within S regions by classical nonhomologous end joining (C-NHEJ). Instead, we find that MMSET-II inactivation leads to decreased AID recruitment and DSBs at the upstream donor S? region. Our findings suggest a role for the HMT MMSET in promoting AID-mediated DNA breaks during CSR.


PROVIDER: S-EPMC5724247 | BioStudies | 2017-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5789958 | BioStudies
2018-01-08 | GSE106922 | GEO
1000-01-01 | S-EPMC4260585 | BioStudies
2018-01-01 | S-EPMC6305588 | BioStudies
2013-01-01 | S-EPMC3832931 | BioStudies
2010-01-01 | S-EPMC2840363 | BioStudies
2008-01-01 | S-EPMC2275379 | BioStudies
2008-01-01 | S-EPMC2585838 | BioStudies
2019-01-01 | S-EPMC6856444 | BioStudies
2019-01-01 | S-EPMC6467426 | BioStudies