Abstract:
:Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in various embryonic and adult tissues. Mice mutant for either Tet1 or Tet2 are viable, raising the question of whether these enzymes have overlapping roles in development. Here we have generated Tet1 and Tet2 double-knockout (DKO) embryonic stem cells (ESCs) and mice. DKO ESCs remained pluripotent but were depleted of 5hmC and caused developmental defects in chimeric embryos. While a fraction of double-mutant embryos exhibited midgestation abnormalities with perinatal lethality, viable and overtly normal Tet1/Tet2-deficient mice were also obtained. DKO mice had reduced 5hmC and increased 5mC levels and abnormal methylation at various imprinted loci. Nevertheless, animals of both sexes were fertile, with females having smaller ovaries and reduced fertility. Our data show that loss of both enzymes is compatible with development but promotes hypermethylation and compromises imprinting. The data also suggest a significant contribution of Tet3 to hydroxylation of 5mC during development.
journal_name
Dev Celljournal_title
Developmental cellauthors
Dawlaty MM,Breiling A,Le T,Raddatz G,Barrasa MI,Cheng AW,Gao Q,Powell BE,Li Z,Xu M,Faull KF,Lyko F,Jaenisch Rdoi
10.1016/j.devcel.2012.12.015subject
Has Abstractpub_date
2013-02-11 00:00:00pages
310-23issue
3eissn
1534-5807issn
1878-1551pii
S1534-5807(12)00589-8journal_volume
24pub_type
杂志文章abstract::Protein transport between the ER and the Golgi in mammalian cells occurs via large pleiomorphic carriers, and most current models suggest that these are formed by the fusion of small ER-derived COPII vesicles. We have examined the dynamics and structural features of these carriers during and after their formation from...
journal_title:Developmental cell
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doi:10.1016/s1534-5807(03)00294-6
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abstract::RhoA stimulates cell contractility by recruiting downstream effectors to the cortical plasma membrane. We now show that direct binding by anillin is required for effective signaling: this antagonizes the otherwise labile membrane association of GTP-RhoA to promote effector recruitment. However, since its binding to Rh...
journal_title:Developmental cell
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abstract::Studies of myoblast fusion in Drosophila have revealed numerous signaling and structural proteins that regulate this critical event in muscle development. A paper by Chen et al. published in the September 19 issue of Cell adds ARF6, a GTPase, and one of its guanine nucleotide exchange factors to this set of players. ...
journal_title:Developmental cell
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doi:10.1016/s1534-5807(03)00298-3
更新日期:2003-10-01 00:00:00
abstract::Two cell cycle surveillance systems--the DNA damage checkpoint and the spindle checkpoint--guard against genomic instability. The protein kinase Chk1 is a well-established signal transducer in the DNA damage checkpoint. In this issue of Developmental Cell, Zachos et al.(2007) present evidence to indicate that Chk1 als...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2007.01.005
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journal_title:Developmental cell
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abstract::Mitochondrial fission mediated by the GTPase dynamin-related protein 1 (Drp1) is an attractive drug target in numerous maladies that range from heart disease to neurodegenerative disorders. The compound mdivi-1 is widely reported to inhibit Drp1-dependent fission, elongate mitochondria, and mitigate brain injury. Here...
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pub_type: 杂志文章
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abstract::The Decapentaplegic and Notch signaling pathways are thought to direct regional specification in the Drosophila eye-antennal epithelium by controlling the expression of selector genes for the eye (Eyeless/Pax6, Eyes absent) and/or antenna (Distal-less). Here, we investigate the function of these signaling pathways in ...
journal_title:Developmental cell
pub_type: 杂志文章
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更新日期:2003-09-01 00:00:00
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journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.10.024
更新日期:2010-01-19 00:00:00
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journal_title:Developmental cell
pub_type: 评论,杂志文章
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journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.05.008
更新日期:2015-07-06 00:00:00
abstract::SAG/RBX2/ROC2 protein is an essential RING component of SCF E3 ubiquitin ligase. The role of SAG during embryogenesis remains unknown. We report a critical role for SAG in controlling vascular and neural development by modulating RAS activity via promoting degradation of neurofibromatosis type 1 (NF1). Mice mutant for...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.09.014
更新日期:2011-12-13 00:00:00
abstract::Netrin-1 was recently proposed to play an important role in embryonic and pathological angiogenesis. However, data reported led to the apparently contradictory conclusions that netrin-1 is either a pro- or an antiangiogenic factor. Here, we reconcile these opposing observations by demonstrating that netrin-1 acts as a...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.02.006
更新日期:2009-04-01 00:00:00
abstract::Metastasizing breast carcinoma cells have been hypothesized to mobilize tissue-invasive activity by co-opting the proteolytic systems employed by normal mammary epithelial cells undergoing branching morphogenesis. However, the critical effectors underlying morphogenesis remain unidentified, and their relationship to b...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.08.025
更新日期:2018-10-22 00:00:00
abstract::Gap junctions are present in most tissues and play essential roles in various biological processes. However, we know surprisingly little about the molecular mechanisms underlying gap junction formation. Here, we uncover the essential role of a conserved EGF- and laminin-G-domain-containing protein nlr-1/CASPR in the r...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2020.10.020
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journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.05.014
更新日期:2012-07-17 00:00:00
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journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2013.04.004
更新日期:2013-04-29 00:00:00
abstract::Mutations in Pkd1, encoding polycystin-1 (PC1), cause autosomal-dominant polycystic kidney disease (ADPKD). We show that the carboxy-terminal tail (CTT) of PC1 is released by γ-secretase-mediated cleavage and regulates the Wnt and CHOP pathways by binding the transcription factors TCF and CHOP, disrupting their intera...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.10.028
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journal_title:Developmental cell
pub_type: 杂志文章
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更新日期:2019-09-23 00:00:00
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journal_title:Developmental cell
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更新日期:2002-10-01 00:00:00
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journal_title:Developmental cell
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journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2005.03.006
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journal_title:Developmental cell
pub_type: 评论,杂志文章
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journal_title:Developmental cell
pub_type: 评论,杂志文章
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abstract::Endoplasmic reticulum-plasma membrane (ER-PM) junctions are conserved structures defined as regions of the ER that tightly associate with the plasma membrane. However, little is known about the mechanisms that tether these organelles together and why such connections are maintained. Using a quantitative proteomic appr...
journal_title:Developmental cell
pub_type: 杂志文章
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更新日期:2012-12-11 00:00:00
abstract::Vertebrate hematopoiesis first produces primitive (embryonic) lineages and ultimately generates the definitive (adult) blood. Whereas definitive hematopoiesis may produce many diverse blood types via a common multipotent progenitor, primitive hematopoiesis has been thought to produce only erythrocytes or macrophages v...
journal_title:Developmental cell
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doi:10.1016/j.devcel.2009.04.007
更新日期:2009-05-01 00:00:00
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journal_title:Developmental cell
pub_type: 杂志文章
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更新日期:2006-07-01 00:00:00
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journal_title:Developmental cell
pub_type: 传,社论,历史文章
doi:10.1016/j.devcel.2007.11.012
更新日期:2007-12-01 00:00:00
abstract::Inherited mtDNA mutations cause severe human disease. In most species, mitochondria are inherited maternally through mechanisms that are poorly understood. Genes that specifically control the inheritance of mitochondria in the germline are unknown. Here, we show that the long isoform of the protein Oskar regulates the...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2016.11.004
更新日期:2016-12-05 00:00:00