title: Reduced dosage of the modifiers of epigenetic reprogramming Dnmt1, Dnmt3L, SmcHD1 and Foxo3a has no detectable effect on mouse telomere length in vivo.
abstract: Studies carried out in cultured cells have implicated modifiers of epigenetic reprogramming in the regulation of telomere length, reporting elongation in cells that were null for DNA methyltransferase DNA methyltransferase 1 (Dnmt1), both de novo DNA methyltransferases, Dnmt3a and Dnmt3b or various histone methyltransferases. To investigate this further, we assayed telomere length in whole embryos or adult tissue from mice carrying mutations in four different modifiers of epigenetic reprogramming: Dnmt1, DNA methyltransferase 3-like, structural maintenance of chromosomes hinge domain containing 1, and forkhead box O3a. Terminal restriction fragment analysis was used to compare telomere length in homozygous mutants, heterozygous mutants and wild-type littermates. Contrary to expectation, we did not detect overall lengthening in the mutants, raising questions about the role of epigenetic processes in telomere length in vivo.
authors.affiliation: Epigenetics Laboratory, Queensland Institute of Medical Research, Herston, QLD, Australia.
authors.forename: Amity R
authors.initials: AR
authors.lastname: Roberts
authors.forename: Marnie E
authors.initials: ME
authors.lastname: Blewitt
authors.forename: Neil A
authors.initials: NA
authors.lastname: Youngson
authors.forename: Emma
authors.initials: E
authors.lastname: Whitelaw
authors.forename: Suyinn
authors.initials: S
authors.lastname: Chong
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency / Q000235:genetics*; D019175:DNA Methylation; D004587:Electrophoresis, Agar Gel; D004622:Embryo, Mammalian; D057890:Epigenomics; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics*; D018628:Gene Dosage; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D011247:Pregnancy; D015183:Restriction Mapping; D016615:Telomere / Q000737:chemistry* / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C529024:SmcHD1 protein, mouse; C498796:Dnmt3l protein, mouse; D000076983:Histone Methyltransferases; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse; D011495:Histone-Lysine N-Methyltransferase