CHAPTER 12: 2-Oxoglutarate-Dependent Hydroxylases Involved in DNA Base J (β-D-Glucopyranosyloxymethyluracil) Synthesis

Base J (β-D-glucopyranosyloxymethyluracil) is an O-linked glycosylated thymine found in the nuclear DNA of flagellated protozoa of the order Kinetoplastida, where this epigenetic mark replaces ∼1% of the total thymidine. Base J synthesis is initiated at specific sites within the genome by the hydroxylation of thymidine using the Fe(ii)/2-oxoglutarate-dependent dioxygenases JBP1 and JBP2, forming hydroxymethyl uracil (hmU), followed by the glucosylation of hmU using a glucosyltransferase. This epigenetic modification has been shown to regulate chromatin structure and RNA polymerase II transcription in kinetoplastid parasites. Here we describe our current knowledge of the structure and function of the two dioxygenases, focusing on how they regulate base J synthesis and how this has been pivotal in unravelling the function of this unusual epigenetic mark. Finally, we discuss how the parasite may utilize characteristics of the dioxygenase to epigenetically regulate gene expression in response to environmental changes within the host.