Lessons from DNMT3L Dependent Methylation During Gametogenesis
Sarah A. Kinkel and Hamish S. Scott
from: Epigenetics: A Reference Manual (Edited by: Jeffrey M. Craig and Nicholas C. Wong). Caister Academic Press, U.K. (2011)
DNMT3L (DNA methyltransferase 3 like) is member of the DNA methyltransferase family of enzymes responsible for the methylation of CpG dinucleotides. Biochemical studies have revealed that while DNMT3L lacks DNA methyltransferase activity, it can bind to and stimulate the activity of de novo DNA methyltransferases DNMT3A and DNMT3B. DNMT3L has also been shown to interact directly with chromatin via its plant homeodomain (PHD)-like zinc finger domain. Studies in Dnmt3L-deficient mice have revealed that DNMT3L is essential for establishing correct methylation patterns at RetroTransposable Elements (RTE), unique loci and parentally imprinted genes in germ cells, and mice without DNMT3L are rendered infertile. Female Dnmt3L-/- mice have apparently normal meiosis but in male Dnmt3L-/- germ cells there is asynapsis of chromosomes, and "meiotic catastrophe". Dnmt3L was among the first mammalian genes shown to have a paternal effect, where the genotype of the father (Dnmt3L+/-) affects sex chromosome aneuploidy in adult and embryonic offspring. This chapter will discuss the role of DNMT3L in establishing DNA methylation patterns during gametogenesis, as well as the proven and potential consequences of DNMT3L-deficiency to fertility and somatic and germline genetic disease in light of the increasing evidence that epigenetic reprogramming is a dose sensitive and partially stochastic process read more ...