Abstract:
:Epigenetic modifications of chromatin play an important role in the regulation of gene expression. KMT4/Dot1 is a conserved histone methyltransferase capable of methylating chromatin on Lys79 of histone H3 (H3K79). Here we report the identification of a multisubunit Dot1 complex (DotCom), which includes several of the mixed lineage leukemia (MLL) partners in leukemia such as ENL, AF9/MLLT3, AF17/MLLT6, and AF10/MLLT10, as well as the known Wnt pathway modifiers TRRAP, Skp1, and beta-catenin. We demonstrated that the human DotCom is indeed capable of trimethylating H3K79 and, given the association of beta-catenin, Skp1, and TRRAP, we investigated, and found, a role for Dot1 in Wnt/Wingless signaling in an in vivo model system. Knockdown of Dot1 in Drosophila results in decreased expression of a subset of Wingless target genes. Furthermore, the loss of expression for the Drosophila homologs of the Dot1-associated proteins involved in the regulation of H3K79 shows a similar reduction in expression of these Wingless targets. From yeast to human, specific trimethylation of H3K79 by Dot1 requires the monoubiquitination of histone H2B by the Rad6/Bre1 complex. Here, we demonstrate that depletion of Bre1, the E3 ligase required for H2B monoubiquitination, leads specifically to reduced bulk H3K79 trimethylation levels and a reduction in expression of many Wingless targets. Overall, our study describes for the first time the components of DotCom and links the specific regulation of H3K79 trimethylation by Dot1 and its associated factors to the Wnt/Wingless signaling pathway.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Mohan M,Herz HM,Takahashi YH,Lin C,Lai KC,Zhang Y,Washburn MP,Florens L,Shilatifard Adoi
10.1101/gad.1898410subject
Has Abstractpub_date
2010-03-15 00:00:00pages
574-89issue
6eissn
0890-9369issn
1549-5477pii
gad.1898410journal_volume
24pub_type
杂志文章abstract::Chromatin-modifying enzymes are known to be critical components for the correct differentiation of embryonic stem cells into specific lineages, such as neurons. Recently, the role of Polycomb group proteins has been studied in the specification and differentiation of muscle stem cells. In this perspective, we review a...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.2054311
更新日期:2011-05-15 00:00:00
abstract::RNA polymerase II nascent transcripts are capped during pausing before elongation. Here we report that hSPT5, the human homolog of yeast elongation factor SPT5, interacts directly with the capping enzyme. hSPT5 stimulated capping enzyme guanylylation and mRNA capping by severalfold. Although RNA 5'-triphosphatase acti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.14.1774
更新日期:1999-07-15 00:00:00
abstract::Transcriptionally silent genes must be activated throughout development. This requires nucleosomes be removed from promoters and enhancers to allow transcription factor (TF) binding and recruitment of coactivators and RNA polymerase II (Pol II). Specialized pioneer TFs bind nucleosome-wrapped DNA to perform this chrom...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.341768.120
更新日期:2021-01-01 00:00:00
abstract::RNAi has revolutionized reverse genetics; however, RNAi is not necessarily ubiquitous or constitutive. Lund and colleagues (pp. 1121-1131) show that microRNA (miRNA) effector Argonautes (Agos) are limiting and easily saturated during early Xenopus embryogenesis. Moreover, this stage is devoid of slicing capacity. Supp...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.2062911
更新日期:2011-06-01 00:00:00
abstract::Infection of metazoan cells with some viruses alters the balance of cellular mRNA export to favor viral RNA export and to retain cellular transcripts in the nucleus. Here, evidence is presented to show that the herpes simplex virus 1 (HSV-1) essential regulatory protein ICP27, which inhibits host cell-splicing, result...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.6.868
更新日期:1998-03-15 00:00:00
abstract::DinI is a recently described negative regulator of the SOS response in Escherichia coli. Here we show that it physically interacts with RecA and prevents the binding of single-stranded DNA to RecA, which is required for the activation of the latter. DinI also displaces ssDNA from a stable RecA-DNA cofilament, thus eli...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.862901
更新日期:2001-02-15 00:00:00
abstract::Direct reprogramming of fibroblasts to cardiomyocytes represents a potential means of restoring cardiac function following myocardial injury. AKT1 in the presence of four cardiogenic transcription factors, GATA4, HAND2, MEF2C, and TBX5 (AGHMT), efficiently induces the cardiac gene program in mouse embryonic fibroblast...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.305482.117
更新日期:2017-09-01 00:00:00
abstract::Transcriptional repressors play a key role in establishing localized patterns of gene expression in the early Drosophila embryo. Several different modes of repression have been implicated in previous studies, including competition and direct interference with the transcription complex. Here, we present evidence for "q...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.15.1829
更新日期:1994-08-01 00:00:00
abstract::The discovery of transcription factors (TFs) controlling pathways in health and disease is of paramount interest. We designed a widely applicable method, dubbed barcorded synthetic tandem repeat promoter screening (BC-STAR-PROM), to identify signal-activated TFs without any a priori knowledge about their properties. T...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.284828.116
更新日期:2016-08-15 00:00:00
abstract::Joints form within the developing skeleton through the segmentation and cavitation of initially continuous cartilage condensations. However, the molecular pathways controlling joint formation largely remain to be clarified. In particular, while several critical secreted signals have been identified, no transcription f...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.209239.112
更新日期:2013-03-01 00:00:00
abstract::The gene encoding yeast U6 snRNA that is transcribed by RNA polymerase III (Pol III) contains both a TATA box upstream of the transcription start site and a downstream binding site for the factor TFIIIC. This juxtaposition of elements typical of both Pol II- and Pol III-transcribed genes raises the question of how pol...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.7.832
更新日期:1995-04-01 00:00:00
abstract::Mediator was resolved from yeast as a multiprotein complex on the basis of its requirement for transcriptional activation in a fully defined system. Three groups of mediator polypeptides could be distinguished: the products of five SRB genes, identified as suppressors of carboxy-terminal domain (CTD)-truncation mutant...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.1.45
更新日期:1998-01-01 00:00:00
abstract::The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the ex...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.294104
更新日期:2004-05-15 00:00:00
abstract::Multiple DNA repair pathways maintain genome stability and ensure that DNA remains essentially unchanged over the life of a cell. Various human diseases occur if DNA repair is compromised, and most of these impact the nervous system, in some cases exclusively. However, it is often unclear what specific endogenous dama...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.301325.117
更新日期:2017-06-15 00:00:00
abstract::We have developed a simple, effective genetic screen for mutant alleles of eukaryotic DNA topoisomerase I that manifest severely depressed or complete loss of enzymatic function. The screen is based on the extreme toxicity of vaccinia topoisomerase expression in the Escherichia coli lysogen strain BL21(DE3) and is not...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.515
更新日期:1990-04-01 00:00:00
abstract::The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a tran...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.284729.116
更新日期:2016-08-15 00:00:00
abstract::Kinase suppressor of Ras (KSR) is a recently identified component of Ras-dependent signaling pathways. In this report, we show that murine KSR1 (mKSR1) cooperates with activated Ras to promote Xenopus oocyte maturation and cellular transformation and provide evidence that this cooperation occurs by accelerating mitoge...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.21.2684
更新日期:1996-11-01 00:00:00
abstract::To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1989110
更新日期:2010-12-01 00:00:00
abstract::Deletions and other chromosomal rearrangements can be generated by recombination between repeated sequences. It has been shown in a number of systems that the probability of exchange or gene conversion decreases with increasing distance between repeats. This paper examines the question of how repeats find each other, ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1800
更新日期:1988-12-01 00:00:00
abstract::The hair follicle undergoes a lifelong developmental cycle that depends on the integration between activating and inhibitory signals acting to regulate and guide the proliferation and differentiation of pluripotent epithelial stem cells. The effectors and mechanisms responsible for re-entry of quiescent telogen hair f...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.223172.113
更新日期:2013-06-15 00:00:00
abstract::The number of known long noncoding RNA (lncRNA) functions is rapidly growing, but how those functions are encoded in their sequence and structure remains poorly understood. NORAD (noncoding RNA activated by DNA damage) is a recently characterized, abundant, and highly conserved lncRNA that is required for proper mitot...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.309138.117
更新日期:2018-01-01 00:00:00
abstract::VASA is an evolutionarily conserved RNA helicase essential for germ cell development. The mouse PIWI family proteins MILI and MIWI2 are involved in production of Piwi-interacting RNAs (piRNAs) in fetal male germ cells through a ping-pong amplification cycle. Expression of retrotransposons is elevated in MILI- and MIWI...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1902110
更新日期:2010-05-01 00:00:00
abstract::We report the discovery of mRNA 5'-leader trans-splicing (SL trans-splicing) in the chordates. In the ascidian protochordate Ciona intestinalis, the mRNAs of at least seven genes undergo trans-splicing of a 16-nucleotide 5'-leader apparently derived from a 46-nucleotide RNA that shares features with previously charact...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.865401
更新日期:2001-02-01 00:00:00
abstract::Discrete sequence elements known as exonic splicing enhancers (ESEs) have been shown to influence both the efficiency of splicing and the profile of mature mRNAs in multicellular eukaryotes. While the existence of ESEs has not been demonstrated previously in unicellular eukaryotes, the factors known to recognize these...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1265905
更新日期:2005-01-15 00:00:00
abstract::Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erbalpha tightly controls the level of its own lig...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1825809
更新日期:2009-09-15 00:00:00
abstract::We used Sarkosyl to analyze steps along the pathway of transcription initiation by RNA polymerase III. Sarkosyl (0.015%) inhibited transcription when present prior to incubation of RNA polymerase III, TFIIIB, and TFIIIC with the VAI gene, whereas it had no detectable effect on initiation or reinitiation of transcripti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.4.646
更新日期:1990-04-01 00:00:00
abstract::Sensory organ formation in Drosophila is activated by proneural genes that encode basic-helix-loop-helix (bHLH) transcription factors. These genes are antagonized by hairy and other proline-bHLH proteins. hairy has not been shown to bind to DNA and has been proposed to form inactive heterodimers with proneural activat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.22.2743
更新日期:1994-11-15 00:00:00
abstract::The yeast HO gene is transcribed transiently during G1 as cells undergo START. START-specific HO activation requires two proteins, SWI4 and SWI6, which act via a motif (CACGA4) repeated up to 10 times within the URS2 region of the HO promoter. We identified a DNA-binding activity containing SWI4 and SWI6 that recogniz...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.11.2000
更新日期:1991-11-01 00:00:00
abstract::Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.281030.116
更新日期:2016-08-01 00:00:00
abstract::All multisubunit DNA-dependent RNA polymerases (RNAP) are zinc metalloenzymes, and at least two zinc atoms are present per enzyme molecule. RNAP residues involved in zinc binding and the functional role of zinc ions in the transcription mechanism or RNAP structure are unknown. Here, we locate four cysteine residues in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.18.2439
更新日期:1999-09-15 00:00:00