Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Histone methylations have been implicated to play important roles in diverse cellular processes. Of particular interest is the methylation of histone H3K79, which is catalyzed by an evolutionarily conserved methyltransferase, disruptor of telomeric silencing (Dot1)-like (Dot1L). To investigate the role of Dot1L during vertebrate development, we have generated a Dot1L-specific transcription activator-like effector nuclease (TALEN) nuclease to knockdown endogenous Dot1L in Xenopus tropicalis, a diploid species highly related to the well-known developmental model Xenopus laevis, a pseudotetraploid amphibian. We show that the TALEN was extremely efficient in mutating Dot1L when expressed in fertilized eggs, creating essentially Dot1L knockout embryos with little H3K79 methylation. Importantly, we observed that Dot1L knockdown had no apparent effect on embryogenesis because normally feeding tadpoles were formed, consistent with the lack of maternal Dot1L expression. On the other hand, Dot1L knockdown severely retarded the growth of the tadpoles and led to tadpole lethality prior to metamorphosis. These findings suggest that Dot1L and H3K79 methylation play an important role for tadpole growth and development prior to metamorphosis into a frog. Our findings further reveal interesting similarities and differences between Xenopus and mouse development and suggest the existence of 2 separate phases of vertebrate development with distinct requirements for epigenetic modifications.
Barry,
Targeting DOT1L action and interactions in leukemia: the role of DOT1L in transformation and development.
2010, Pubmed
Barry,
Targeting DOT1L action and interactions in leukemia: the role of DOT1L in transformation and development.
2010,
Pubmed
Barski,
High-resolution profiling of histone methylations in the human genome.
2007,
Pubmed
Barth,
Fast signals and slow marks: the dynamics of histone modifications.
2010,
Pubmed
Cao,
Role of histone H3 lysine 27 methylation in Polycomb-group silencing.
2002,
Pubmed
Cao,
Tissue-specific expression of an Ornithine decarboxylase paralogue, XODC2, in Xenopus laevis.
2001,
Pubmed
,
Xenbase
Cao,
The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3.
2004,
Pubmed
Dillon,
The SET-domain protein superfamily: protein lysine methyltransferases.
2005,
Pubmed
Feng,
Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain.
2002,
Pubmed
Greer,
Histone methylation: a dynamic mark in health, disease and inheritance.
2012,
Pubmed
Hasebe,
Thyroid hormone-induced cell-cell interactions are required for the development of adult intestinal stem cells.
2013,
Pubmed
,
Xenbase
Ishizuya-Oka,
Evolutionary insights into postembryonic development of adult intestinal stem cells.
2011,
Pubmed
Jones,
The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure.
2008,
Pubmed
Kouzarides,
Chromatin modifications and their function.
2007,
Pubmed
Lei,
Efficient targeted gene disruption in Xenopus embryos using engineered transcription activator-like effector nucleases (TALENs).
2012,
Pubmed
,
Xenbase
Lei,
Generation of gene disruptions by transcription activator-like effector nucleases (TALENs) in Xenopus tropicalis embryos.
2013,
Pubmed
,
Xenbase
Li,
The role of chromatin during transcription.
2007,
Pubmed
Matsuura,
Liganded thyroid hormone receptor induces nucleosome removal and histone modifications to activate transcription during larval intestinal cell death and adult stem cell development.
2012,
Pubmed
,
Xenbase
Matsuura,
Histone H3K79 methyltransferase Dot1L is directly activated by thyroid hormone receptor during Xenopus metamorphosis.
2012,
Pubmed
,
Xenbase
Maunakea,
Epigenome mapping in normal and disease States.
2010,
Pubmed
Min,
Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase.
2003,
Pubmed
Nguyen,
The diverse functions of Dot1 and H3K79 methylation.
2011,
Pubmed
Ooga,
Changes in H3K79 methylation during preimplantation development in mice.
2008,
Pubmed
Roh,
The genomic landscape of histone modifications in human T cells.
2006,
Pubmed
Shanower,
Characterization of the grappa gene, the Drosophila histone H3 lysine 79 methyltransferase.
2005,
Pubmed
Shi,
Thyroid hormone receptor actions on transcription in amphibia: The roles of histone modification and chromatin disruption.
2012,
Pubmed
Singer,
Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae.
1998,
Pubmed
Tata,
Gene expression during metamorphosis: an ideal model for post-embryonic development.
1993,
Pubmed
Wang,
Combinatorial patterns of histone acetylations and methylations in the human genome.
2008,
Pubmed
Wang,
Characterization of human epigenomes.
2009,
Pubmed
Wen,
Appl1 is essential for the survival of Xenopus pancreas, duodenum, and stomach progenitor cells.
2010,
Pubmed
,
Xenbase
van Leeuwen,
Dot1p modulates silencing in yeast by methylation of the nucleosome core.
2002,
Pubmed
