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.
FASEB J
2017 Nov 01;3111:4821-4831. doi: 10.1096/fj.201700131R.
Show Gene links
Show Anatomy links
Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development.
Wen L
,
Fu L
,
Shi YB
.
???displayArticle.abstract???
Histone modifications are associated with transcriptional regulation by diverse transcription factors. Genome-wide correlation studies have revealed that histone activation marks and repression marks are associated with activated and repressed gene expression, respectively. Among the histone activation marks is histone H3 K79 methylation, which is carried out by only a single methyltransferase, disruptor of telomeric silencing-1-like (DOT1L). We have been studying thyroid hormone (T3)-dependent amphibian metamorphosis in two highly related species, the pseudo-tetraploid Xenopus laevis and diploid Xenopus tropicalis, as a model for postembryonic development, a period around birth in mammals that is difficult to study. We previously showed that H3K79 methylation levels are induced at T3 target genes during natural and T3-induced metamorphosis and that Dot1L is itself a T3 target gene. These suggest that T3 induces Dot1L expression, and Dot1L in turn functions as a T3 receptor (TR) coactivator to promote vertebrate development. We show here that in cotransfection studies or in the reconstituted frog oocyte in vivo transcription system, overexpression of Dot1L enhances gene activation by TR in the presence of T3. Furthermore, making use of the ability to carry out transgenesis in X. laevis and gene knockdown in X. tropicalis, we demonstrate that endogenous Dot1L is critical for T3-induced activation of endogenous TR target genes while transgenic Dot1L enhances endogenous TR function in premetamorphic tadpoles in the presence of T3. Our studies thus for the first time provide complementary gain- and loss-of functional evidence in vivo for a cofactor, Dot1L, in gene activation by TR during vertebrate development.-Wen, L., Fu, L., Shi, Y.-B. Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development.
Amaya,
Frog genetics: Xenopus tropicalis jumps into the future.
1998, Pubmed,
Xenbase
Amaya,
Frog genetics: Xenopus tropicalis jumps into the future.
1998,
Pubmed
,
Xenbase
Bagamasbad,
Deciphering the regulatory logic of an ancient, ultraconserved nuclear receptor enhancer module.
2015,
Pubmed
,
Xenbase
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
Bilesimo,
Specific histone lysine 4 methylation patterns define TR-binding capacity and differentiate direct T3 responses.
2011,
Pubmed
,
Xenbase
Blitz,
Biallelic genome modification in F(0) Xenopus tropicalis embryos using the CRISPR/Cas system.
2013,
Pubmed
,
Xenbase
Buchholz,
A dominant-negative thyroid hormone receptor blocks amphibian metamorphosis by retaining corepressors at target genes.
2003,
Pubmed
,
Xenbase
Buchholz,
Transgenic analysis reveals that thyroid hormone receptor is sufficient to mediate the thyroid hormone signal in frog metamorphosis.
2004,
Pubmed
,
Xenbase
Buchholz,
Molecular and developmental analyses of thyroid hormone receptor function in Xenopus laevis, the African clawed frog.
2006,
Pubmed
,
Xenbase
Burke,
Co-repressors 2000.
2000,
Pubmed
Cao,
The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3.
2004,
Pubmed
Cao,
Role of histone H3 lysine 27 methylation in Polycomb-group silencing.
2002,
Pubmed
Chen,
Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300.
1997,
Pubmed
Choi,
Unliganded thyroid hormone receptor α regulates developmental timing via gene repression in Xenopus tropicalis.
2015,
Pubmed
,
Xenbase
Das,
Identification of direct thyroid hormone response genes reveals the earliest gene regulation programs during frog metamorphosis.
2009,
Pubmed
,
Xenbase
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
Fu,
Genome-wide identification of Xenopus matrix metalloproteinases: conservation and unique duplications in amphibians.
2009,
Pubmed
,
Xenbase
Fu,
Novel double promoter approach for identification of transgenic animals: A tool for in vivo analysis of gene function and development of gene-based therapies.
2002,
Pubmed
,
Xenbase
Fu,
Transcriptional regulation of the Xenopus laevis Stromelysin-3 gene by thyroid hormone is mediated by a DNA element in the first intron.
2006,
Pubmed
,
Xenbase
Fujimoto,
Direct activation of Xenopus iodotyrosine deiodinase by thyroid hormone receptor in the remodeling intestine during amphibian metamorphosis.
2012,
Pubmed
,
Xenbase
Furlow,
The transcription factor basic transcription element-binding protein 1 is a direct thyroid hormone response gene in the frog Xenopus laevis.
2002,
Pubmed
,
Xenbase
Furlow,
In vitro and in vivo analysis of the regulation of a transcription factor gene by thyroid hormone during Xenopus laevis metamorphosis.
1999,
Pubmed
,
Xenbase
Greer,
Histone methylation: a dynamic mark in health, disease and inheritance.
2012,
Pubmed
Guo,
Efficient RNA/Cas9-mediated genome editing in Xenopus tropicalis.
2014,
Pubmed
,
Xenbase
Havis,
Metamorphic T3-response genes have specific co-regulator requirements.
2003,
Pubmed
,
Xenbase
Heimeier,
Participation of Brahma-related gene 1 (BRG1)-associated factor 57 and BRG1-containing chromatin remodeling complexes in thyroid hormone-dependent gene activation during vertebrate development.
2008,
Pubmed
,
Xenbase
Huang,
A role for cofactor-cofactor and cofactor-histone interactions in targeting p300, SWI/SNF and Mediator for transcription.
2003,
Pubmed
,
Xenbase
Ishizuka,
The N-CoR/histone deacetylase 3 complex is required for repression by thyroid hormone receptor.
2003,
Pubmed
Jones,
Multiple N-CoR complexes contain distinct histone deacetylases.
2001,
Pubmed
,
Xenbase
Jones,
The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure.
2008,
Pubmed
Jones,
N-CoR-HDAC corepressor complexes: roles in transcriptional regulation by nuclear hormone receptors.
2003,
Pubmed
,
Xenbase
Kouzarides,
Chromatin modifications and their function.
2007,
Pubmed
Kroll,
Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation.
1996,
Pubmed
,
Xenbase
Lei,
Generation of gene disruptions by transcription activator-like effector nucleases (TALENs) in Xenopus tropicalis embryos.
2013,
Pubmed
,
Xenbase
Li,
Specific targeting and constitutive association of histone deacetylase complexes during transcriptional repression.
2002,
Pubmed
,
Xenbase
Li,
Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3.
2000,
Pubmed
,
Xenbase
Li,
p300 requires its histone acetyltransferase activity and SRC-1 interaction domain to facilitate thyroid hormone receptor activation in chromatin.
2000,
Pubmed
,
Xenbase
Li,
The role of chromatin during transcription.
2007,
Pubmed
Matsuda,
Contrasting effects of two alternative splicing forms of coactivator-associated arginine methyltransferase 1 on thyroid hormone receptor-mediated transcription in Xenopus laevis.
2007,
Pubmed
,
Xenbase
Matsuda,
Novel functions of protein arginine methyltransferase 1 in thyroid hormone receptor-mediated transcription and in the regulation of metamorphic rate in Xenopus laevis.
2009,
Pubmed
,
Xenbase
Matsuda,
An essential and evolutionarily conserved role of protein arginine methyltransferase 1 for adult intestinal stem cells during postembryonic development.
2010,
Pubmed
,
Xenbase
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
McKenna,
Nuclear receptors, coregulators, ligands, and selective receptor modulators: making sense of the patchwork quilt.
2001,
Pubmed
Nakade,
Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9.
2014,
Pubmed
,
Xenbase
Nakajima,
Dual mechanisms governing muscle cell death in tadpole tail during amphibian metamorphosis.
2003,
Pubmed
,
Xenbase
Nakayama,
Simple and efficient CRISPR/Cas9-mediated targeted mutagenesis in Xenopus tropicalis.
2013,
Pubmed
,
Xenbase
Nguyen,
The diverse functions of Dot1 and H3K79 methylation.
2011,
Pubmed
Paul,
Distinct expression profiles of transcriptional coactivators for thyroid hormone receptors during Xenopus laevis metamorphosis.
2003,
Pubmed
,
Xenbase
Paul,
Tissue- and gene-specific recruitment of steroid receptor coactivator-3 by thyroid hormone receptor during development.
2005,
Pubmed
,
Xenbase
Paul,
SRC-p300 coactivator complex is required for thyroid hormone-induced amphibian metamorphosis.
2007,
Pubmed
,
Xenbase
Paul,
Coactivator recruitment is essential for liganded thyroid hormone receptor to initiate amphibian metamorphosis.
2005,
Pubmed
,
Xenbase
Ranjan,
Transcriptional repression of Xenopus TR beta gene is mediated by a thyroid hormone response element located near the start site.
1994,
Pubmed
,
Xenbase
Roh,
The genomic landscape of histone modifications in human T cells.
2006,
Pubmed
Sachs,
Nuclear receptor corepressor recruitment by unliganded thyroid hormone receptor in gene repression during Xenopus laevis development.
2002,
Pubmed
,
Xenbase
Sato,
A role of unliganded thyroid hormone receptor in postembryonic development in Xenopus laevis.
2007,
Pubmed
,
Xenbase
Schreiber,
Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor.
2001,
Pubmed
,
Xenbase
Shanower,
Characterization of the grappa gene, the Drosophila histone H3 lysine 79 methyltransferase.
2005,
Pubmed
Shi,
Heritable CRISPR/Cas9-mediated targeted integration in Xenopus tropicalis.
2015,
Pubmed
,
Xenbase
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
Sterling,
Cytological and morphological analyses reveal distinct features of intestinal development during Xenopus tropicalis metamorphosis.
2012,
Pubmed
,
Xenbase
Strahl,
Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1.
2001,
Pubmed
Tata,
Gene expression during metamorphosis: an ideal model for post-embryonic development.
1993,
Pubmed
Tomita,
Recruitment of N-CoR/SMRT-TBLR1 corepressor complex by unliganded thyroid hormone receptor for gene repression during frog development.
2004,
Pubmed
,
Xenbase
Tomita,
Fusion protein of retinoic acid receptor alpha with promyelocytic leukemia protein or promyelocytic leukemia zinc finger protein recruits N-CoR-TBLR1 corepressor complex to repress transcription in vivo.
2003,
Pubmed
,
Xenbase
Wang,
Combinatorial patterns of histone acetylations and methylations in the human genome.
2008,
Pubmed
Wang,
Developmental regulation and function of thyroid hormone receptors and 9-cis retinoic acid receptors during Xenopus tropicalis metamorphosis.
2008,
Pubmed
,
Xenbase
Wang,
Targeted gene disruption in Xenopus laevis using CRISPR/Cas9.
2015,
Pubmed
,
Xenbase
Wang,
Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor.
2001,
Pubmed
,
Xenbase
Wang,
Characterization of human epigenomes.
2009,
Pubmed
Wen,
Unliganded thyroid hormone receptor α controls developmental timing in Xenopus tropicalis.
2015,
Pubmed
,
Xenbase
Wen,
Histone methyltransferase Dot1L plays a role in postembryonic development in Xenopus tropicalis.
2015,
Pubmed
,
Xenbase
Wen,
Appl1 is essential for the survival of Xenopus pancreas, duodenum, and stomach progenitor cells.
2010,
Pubmed
,
Xenbase
Wong,
Coordinated regulation of and transcriptional activation by Xenopus thyroid hormone and retinoid X receptors.
1995,
Pubmed
,
Xenbase
Wong,
A role for nucleosome assembly in both silencing and activation of the Xenopus TR beta A gene by the thyroid hormone receptor.
1995,
Pubmed
,
Xenbase
Wong,
Determinants of chromatin disruption and transcriptional regulation instigated by the thyroid hormone receptor: hormone-regulated chromatin disruption is not sufficient for transcriptional activation.
1997,
Pubmed
,
Xenbase
Yen,
Unliganded TRs regulate growth and developmental timing during early embryogenesis: evidence for a dual function mechanism of TR action.
2015,
Pubmed
,
Xenbase
Yoon,
Purification and functional characterization of the human N-CoR complex: the roles of HDAC3, TBL1 and TBLR1.
2003,
Pubmed
Zhang,
The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2.
2002,
Pubmed
van Leeuwen,
Dot1p modulates silencing in yeast by methylation of the nucleosome core.
2002,
Pubmed
