Cell-type-specific Regulation Of Dnmt1Stability By Methylation

Methylation is a major posttranslational modification for histones in eukaryotes. Crosstalk between methylation and other posttranslational modifications is important in regulating chromatin structure and gene activity. In addition to histones, several other cellular proteins including transcription factors and tumor suppressor are subject to methylation. The discovery of non-histone protein methylation suggests that this is a common post-translational modification for regulating protein activity. Recent reports show that the methylation of DNMT1(DNA Methyltransferase1) leads to proteasome mediated DNMT1degradation. Here we show that the regulation of Dnmt1stability by methylation is a cell-type-specific phenomenon. We find that the deficiency of LSD1in LNCaP cell results in the decreased protein level of Dnmt1; while in293T and Hela cells, both LSD1and its homologous protein AOF1are involved in regulating the stability of Dnmt1; but in HCT116cell the protein level of Dnmtl isn't affected by knocking down of LSD1. Our findings together with the results from some other groups suggest that LSD1demethylates and stabilizes Dnmt1in some cell lines. This also provides a mechanistic link between the histone methylation and DNA methylation. The findings that cell-type-specific regulation of Dnmtl stability in different cell lines also suggest a much more complicated mechanism in regulating protein stability.