Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase

• DOI: 10.1038/s41467-018-04019-9
• Publication Date: 2018-04-18T16:40:42Z
• Authors: Feng Leng; Jiekai Yu; Chunxiao Zhang; Salvador Alejo; Nam Hoang; Hong Sun; Fei Lu; Hui Zhang
• Keywords: Histone Methylation; DNA methyltransferase; DNMT1

Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis proteins. Here, we report that 142 DNMT1, major DNA methyltransferase preserves epigenetic inheritance methylation patterns during replication, demethylated by LSD1. A methyl-binding protein, L3MBTL3, binds K142-methylated DNMT1 recruits CRL4DCAF5 ubiquitin ligase degrade DNMT1. Both LSD1 PHF20L1 act primarily in S phase prevent degradation L3MBTL3-CRL4DCAF5. Mouse L3MBTL3/MBT-1 deletion causes accumulation increased genomic methylation, late embryonic lethality. contains consensus motif shared many including E2F1, key transcription factor for phase. We show methylation-dependent E2F1 also controlled Our studies elucidate first time mechanism which stability regulated.