Publications by authors named "Johanna M Fowler"
Ten-eleven translocation (TET) enzymes iteratively oxidize 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine to facilitate active genome demethylation. Whether these bases are required to promote replication-coupled dilution or activate base excision repair during mammalian germline reprogramming remains unresolved due to the inability to decouple TET activities. Here, we generated two mouse lines expressing catalytically inactive TET1 (Tet1-HxD) and TET1 that stalls oxidation at 5hmC (Tet1-V).
View Article and Find Full Text PDF5-methylcytosine (5mC) is the most important DNA modification in mammalian genomes. The ideal method for 5mC localization would be both nondestructive of DNA and direct, without requiring inference based on detection of unmodified cytosines. Here we present direct methylation sequencing (DM-Seq), a bisulfite-free method for profiling 5mC at single-base resolution using nanogram quantities of DNA.
View Article and Find Full Text PDFArticle Synopsis
- DNA methylation removal is essential for reprogramming primordial germ cells in mammals, involving TET enzymes which convert 5-methylcytosine into other forms to enable active demethylation.
- Researchers created two mouse models to better understand TET enzyme roles: one with inactive TET1 and another that limits oxidation to 5hmC.
- The study found that TET1's extra-catalytic functions are crucial for managing hypermethylated regions in sperm, while both TET oxidation and iterative processes are necessary for certain imprinted regions during male germline development.