PGC7/Stella protects against DNA demethylation in early embryogenesis.
DNA methylation is an important means of epigenetic gene regulation and must be carefully controlled as a prerequisite for normal early embryogenesis. Although global demethylation occurs soon after fertilization, it is not evenly distributed throughout the genome. Genomic imprinting and epigenetic asymmetry between parental genomes, that is, delayed demethylation of the maternal genome after fertilization, are clear examples of the functional importance of DNA methylation. Here, we show that PGC7/Stella, a maternal factor essential for early development, protects the DNA methylation state of several imprinted loci and epigenetic asymmetry. After determining that PGC7/Stella binds to Ran binding protein 5 (RanBP5; a nuclear transport shuttle protein), mutant versions of the two proteins were used to examine exactly when and where PGC7/Stella functions within the cell. It is likely that PGC7/Stella protects the maternal genome from demethylation only after localizing to the nucleus, where it maintains the methylation of several imprinted genes. These results demonstrate that PGC7/Stella is indispensable for the maintenance of methylation involved in epigenetic reprogramming after fertilization.
Nakamura
Toshinobu
T
Department of Pathology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka 565-0871, Japan. tnakano@patho.med.osaka-u.ac.jp
Arai
Yoshikazu
Y
Umehara
Hiroki
H
Masuhara
Masaaki
M
Kimura
Tohru
T
Taniguchi
Hisaaki
H
Sekimoto
Toshihiro
T
Ikawa
Masahito
M
Yoneda
Yoshihiro
Y
Okabe
Masaru
M
Tanaka
Satoshi
S
Shiota
Kunio
K
Nakano
Toru
T
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D002868:Chromosomal Proteins, Non-Histone; D019175:DNA Methylation; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005306:Fertilization / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D002868:Chromosomal Proteins, Non-Histone; C466105:DPPA3 protein, human; D011506:Proteins