Limits...
Gene activation-associated long noncoding RNAs function in mouse preimplantation development.

Hamazaki N, Uesaka M, Nakashima K, Agata K, Imamura T - Development (2015)

Bottom Line: Expression of these bidirectional promoter-associated noncoding RNAs (pancRNAs) was strongly associated with the upregulation of their cognate genes.Conversely, knockdown of three abundant pancRNAs led to reduced mRNA expression, accompanied by sustained DNA methylation even in the presence of enzymes responsible for DNA demethylation.Thus, this novel class of lncRNAs can modulate the transcription machinery in cis to activate zygotic genes and is important for preimplantation development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics and Global COE Program, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto 606-8502, Japan Division of Basic Stem Cell Biology, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Show MeSH
Epigenetic changes accompanying zygotic pancRNA-mediated gene activation during early mouse development. (A) DNA methylation status of ABA-treated 2-cell embryos. (B) DNA methylation status of Tet2 or Tet3 versus control siRNA-injected embryos. ***P<0.001. (C) A model for pancRNA-mediated gene activation in early mouse development. At the 2-cell stage, pancIl17d expression, together with TET3 and PARP, leads to establishment of the hypomethylated status at the Il17d promoter in a sequence-specific manner, and thus to Il17d mRNA expression starting from the 4-cell stage. When these steps are compromised, apoptosis increases and cell proliferation decreases, adversely affecting embryonic development.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4352986&req=5

DEV116996F6: Epigenetic changes accompanying zygotic pancRNA-mediated gene activation during early mouse development. (A) DNA methylation status of ABA-treated 2-cell embryos. (B) DNA methylation status of Tet2 or Tet3 versus control siRNA-injected embryos. ***P<0.001. (C) A model for pancRNA-mediated gene activation in early mouse development. At the 2-cell stage, pancIl17d expression, together with TET3 and PARP, leads to establishment of the hypomethylated status at the Il17d promoter in a sequence-specific manner, and thus to Il17d mRNA expression starting from the 4-cell stage. When these steps are compromised, apoptosis increases and cell proliferation decreases, adversely affecting embryonic development.

Mentions: A previous study showed that base excision repair (BER) components, including poly(ADP-ribose) polymerase (PARP), contribute to DNA demethylation in preimplantation embryos (Hajkova et al., 2010). Therefore, we added a PARP inhibitor, 3-aminobenzamide (ABA), to the embryo culture medium to clarify whether promoter demethylation requires the BER pathway. The addition of ABA resulted in inhibition of DNA demethylation of the Il17d promoter region at the 2-cell stage (Fig. 6A; supplementary material Fig. S13), leading to downregulation of the partner mRNA (supplementary material Fig. S14). However, the addition of ABA did not change pancRNA expression, suggesting that expression of pancIl17d itself is regulated independently of the BER pathway and DNA methylation.Fig. 6.


Gene activation-associated long noncoding RNAs function in mouse preimplantation development.

Hamazaki N, Uesaka M, Nakashima K, Agata K, Imamura T - Development (2015)

Epigenetic changes accompanying zygotic pancRNA-mediated gene activation during early mouse development. (A) DNA methylation status of ABA-treated 2-cell embryos. (B) DNA methylation status of Tet2 or Tet3 versus control siRNA-injected embryos. ***P<0.001. (C) A model for pancRNA-mediated gene activation in early mouse development. At the 2-cell stage, pancIl17d expression, together with TET3 and PARP, leads to establishment of the hypomethylated status at the Il17d promoter in a sequence-specific manner, and thus to Il17d mRNA expression starting from the 4-cell stage. When these steps are compromised, apoptosis increases and cell proliferation decreases, adversely affecting embryonic development.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352986&req=5

DEV116996F6: Epigenetic changes accompanying zygotic pancRNA-mediated gene activation during early mouse development. (A) DNA methylation status of ABA-treated 2-cell embryos. (B) DNA methylation status of Tet2 or Tet3 versus control siRNA-injected embryos. ***P<0.001. (C) A model for pancRNA-mediated gene activation in early mouse development. At the 2-cell stage, pancIl17d expression, together with TET3 and PARP, leads to establishment of the hypomethylated status at the Il17d promoter in a sequence-specific manner, and thus to Il17d mRNA expression starting from the 4-cell stage. When these steps are compromised, apoptosis increases and cell proliferation decreases, adversely affecting embryonic development.
Mentions: A previous study showed that base excision repair (BER) components, including poly(ADP-ribose) polymerase (PARP), contribute to DNA demethylation in preimplantation embryos (Hajkova et al., 2010). Therefore, we added a PARP inhibitor, 3-aminobenzamide (ABA), to the embryo culture medium to clarify whether promoter demethylation requires the BER pathway. The addition of ABA resulted in inhibition of DNA demethylation of the Il17d promoter region at the 2-cell stage (Fig. 6A; supplementary material Fig. S13), leading to downregulation of the partner mRNA (supplementary material Fig. S14). However, the addition of ABA did not change pancRNA expression, suggesting that expression of pancIl17d itself is regulated independently of the BER pathway and DNA methylation.Fig. 6.

Bottom Line: Expression of these bidirectional promoter-associated noncoding RNAs (pancRNAs) was strongly associated with the upregulation of their cognate genes.Conversely, knockdown of three abundant pancRNAs led to reduced mRNA expression, accompanied by sustained DNA methylation even in the presence of enzymes responsible for DNA demethylation.Thus, this novel class of lncRNAs can modulate the transcription machinery in cis to activate zygotic genes and is important for preimplantation development.

View Article: PubMed Central - PubMed

Affiliation: Department of Biophysics and Global COE Program, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto 606-8502, Japan Division of Basic Stem Cell Biology, Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Show MeSH