As observed with DNMT3B
, transcription of DNMT3A1 occurs at two distinct promoter regions, both of which have differing levels of CpG content .
Knockdown of three DNA methyltransferases (DNMT1, DNMT3a, and DNMT3B
) also upregulated COX1 and induced senescence in MSCs.
Because genetic variation in methyl transferase and demethylases may directly alter the dynamic processes of methylation, we further investigated whether 262 SNPs in or near DNMT1, DNMT3A, DNMT3B
, DNMT3L, TET1, TET2, TET3, and TDG altered the associations between first-trimester air pollutants and LINE1 methylation.
To examine whether the altered methylation patterns in SVs from mice treated neonatally with DES might be affected by the expression level of the epigenetic modifiers, we used realtime PCR to investigate the RNA levels of DNA methyltransferases, including DNMTs (DNMT1, DNMT3A, and DNMT3B
) and MBDs (MeCP2, MBD2, and MBD3), as well as two histone modifiers (HDAC1 and HDAC2).
Apart from AS3MT and N6AMT1, we have previously reported evidence that genetic variation in DNA methyltransferases DNMT1 and DNMT3B
influences arsenic metabolism efficiency, and similar to N6AMT1, associations with these methyltransferases were weaker than associations with AS3MT variants (Engstrom et al.
DNMT3A, a de novo DNA methyltransferase, establishes the patterns of methylation in early embryonic development, along with DNMT3B
, and cooperates with DNMT1 to maintain the methylation of repetitive sequences such as LINE-1 and Alu elements (Jones and Liang 2009).
Cadmium was inversely associated with DNMT3B
([r.sub.s] = -0.28,p = 0.0086) but not with DNMT1 expression ([r.sub.s] = -0.075,p = 0.48).
KEY WORDS: arsenic, AS3MT, BHMT, DNMT1a, DNMT3b
, gene expression, methylation, one-carbon metabolism, PEMT, polymorphism.
Primers were designed for DNMT1, DNMT3a, DNMT3b
, MBD2, and [beta]-actin and were synthesized by Invitrogen (Carlsbad, CA) as follows: DNMT1 (gi: 6684524) (5'-ACCAAGCAAGAAGTGAAGCC- 3' and 5'-GCTTCCTGCAGAAGAACCTG- 3'), product size: 366 bp; DNMT3a (gi:18033252) (5'- C A C A C A G A A G C A T A T C CAGGAGTG-3' and 5'-AGTGACTGGGA AACCAAATACCC-3'), product size: 551 bp; DNMT3b
(gi: 18033254) (5'-AATGTGAATCCAGCCAGGAAAGGC- 3'and 5'- ACTGGATTACACTCCAGGAACCGT-3') product size: 190 bp; [beta]-actin (5'-AGAGATGGCCACGGCTGCTT- 3' and 5'-ATTTGC GGTGGACGATGGAG-3'), product size: 460 bp.
IL-10 instead activates STAT3, a protein that works as a gene regulator, which in turn increases expression of two genes - DNMT1 and DNMT3b
- in the colon.
Four main variants of DNMTs are found in humans, namely DNMT1, DNMT3A, DNMT3B
, and DNMT3L, to mediate the methylation process.
These investigators indicated that these preclinical results are promising for treating refractory TGCT patients with guadecitabine alone or with cisplatin, because the sensitivity of EC cells to guadecitabine depends on the high level of DNMT3B
expression in EC cells (34).