Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L
. J Biol Chem.2006;281(36):25893-902.
Four main variants of DNMTs are found in humans, namely DNMT1, DNMT3A, DNMT3B, and DNMT3L
, to mediate the methylation process.
Furthermore, IPA identified DNMT3L
as one of the top five upstream regulators of genes overlapping DMRs in newborn cord blood (p = 2.1 x [10.sup.-3] as calculated by IPA using the right-tailed Fisher's exact test) (Table 3).
Epigenetic modification plays an important role in gametogenesis, it has been reported the absence of DNA methyltransferase 3-like (Dnmt3L
) caused overall loss of cytosine-guanine (CG) and non-CG methylation in germ cells and resulted in infertility.
A total of 5 different forms of DNMT, namely, DNMT1, DNMT2, DNMT3a, DNMT3b, and DNMT3L
, have been defined in mammals.
El4.5'te, erkek germ hucrelerinde DNA metiltransferaz DNMT3A ve DNMT3B, ve kofaktor DNMT3L
(DNA methyltransferase 3-like) aktivasyonu ile global de novo DNA metilasyon orani yaklasik %10'dan %50'ye kadar hizla yukselmektedir (11).
Memelilerde 4 farkli DNMT enzimi (DNMT1, DNMT3A, DNMT3B, DNMT3L
) bilinmektedir ve kanser gelisiminde en onemli olani DNMT1'dir (13).
Genes encoding proteins related to immune pathway (DUSP10), cell signaling (PLA2G4A, PRKCD), epigenetic regulation (DNMT3L
, H2AFZ, MBD3), cell differentiation (LIF), cell adhesion and signal transduction (ITGAV), metabolic pathway (RASL 12), and cell apoptosis (FAS) were differentially expressed among the three groups, consistent with the results determined using RNA-Seq.
By contrast, DNMT3L
has no catalytic domain and predominantly functions as an accessory protein to DNMT3A .
The de novo DNA methytransferases DNMT3A and DNMT3B, as well as the co-factor DNMT3L
, are major players in the general mechanisms underlying DNA methylation, (72-75) but the locus specificity is not explained by this alone.
A regulatory factor similar to DNMT3 enzyme is placed beside these enzymes which is referred to as DNMT3L