The histone methyltransferase MMSET regulates class switch recombination.

[wolf-hirschhorn syndrome]

Wolf-Hirschhorn syndrome (WHS ) is a genetic disease with characteristic facial features and developmental disorders . Of interest , loss of the MMSET gene (also known as WHSC 1 ) is considered to be responsible for the core phenotypes of this disease . Patients with WHS also display Ab deficiency , although the underlying cause of this deficiency is unclear . Recent studies suggest that the histone methyltransferase activity of MMSET plays an important role in the DNA damage response by facilitating the recruitment of 53 BP 1 to sites of DNA damage . We hypothesize that MMSET also regulates class switch recombination (CSR ) through its effect on 53 BP 1 . In this study , we show that MMSET indeed plays an important role in CSR through its histone methyltransferase activity . Knocking down MMSET expression impaired 53 BP 1 recruitment as well as the germline transcription of the Igh switch regions , resulting in defective CSR but no effect on cell growth and viability . These results suggest that defective CSR caused by MMSET deficiency could be a cause of Ab deficiency in WHS patients .