One-codon alternative splicing of the CpG MTase Dnmt1 transcript in mouse somatic cells

Area of Science:

• Genetics
• Molecular Biology
• Epigenetics

Background:

• Genomic methylation patterns in mammalian somatic cells are primarily attributed to a single enzyme, DNMT1.
• The DNA (cytosine-5)-methyltransferase, or CpG MTase, is encoded by the Dnmt1 gene in mice.

Purpose of the Study:

• To investigate the molecular mechanisms underlying DNMT1 expression in mammalian somatic cells.
• To determine if alternative splicing of the Dnmt1 gene transcript occurs and generates different protein isoforms.

Main Methods:

• Analysis of Dnmt1 gene transcripts in various mouse tissues and cell types.
• Identification and characterization of alternative splicing events in Dnmt1 mRNA.
• Comparison of the encoded CpG MTase isozymes.

Main Results:

• The primary transcript of the mouse Dnmt1 gene undergoes alternative splicing.
• Two distinct poly-(A) RNAs of similar abundance are generated through alternative splicing.
• This splicing originates from two closely spaced acceptor sites, resulting in two CpG MTase isozymes differing by two amino acids.

Conclusions:

• Mammalian somatic cells possess two DNMT1 isozymes, not a single enzyme as previously assumed.
• The discovery of two Dnmt1 isozymes necessitates a re-evaluation of epigenetic maintenance mechanisms in both mouse and human cells.