Faculty Opinions recommendation of Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain.

2011 ◽  
Author(s):  
Giovanni Neri ◽  
Elisabetta Tabolacci
Keyword(s):  
Dna Demethylation ◽  
Adult Brain ◽  
Active Dna Demethylation

scholarly journals Tet1 isoforms differentially regulate gene expression, synaptic transmission and memory in the mammalian brain

2020 ◽  
Author(s):  
C.B. Greer ◽  
J. Wright ◽  
J.D. Weiss ◽  
R.M. Lazerenko ◽  
S.P. Moran ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Neurons ◽  
Dna Demethylation ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Dynamic Regulation ◽  
Regulate Gene Expression ◽  
Active Dna Demethylation ◽  
Cell Type Specific ◽  
The Individual

The dynamic regulation of DNA methylation in post-mitotic neurons is necessary for memory formation and other adaptive behaviors. Ten-eleven translocation 1 (TET1) plays a part in these processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby initiating active DNA demethylation. However, attempts to pinpoint its exact role in the nervous system have been hindered by contradictory findings, perhaps due in part, to a recent discovery that two isoforms of the Tet1 gene are differentially expressed from early development into adulthood. Here, we demonstrate that both the shorter transcript (Tet1S) encoding an N-terminally truncated TET1 protein and a full-length Tet1 (Tet1FL) transcript encoding canonical TET1 are co-expressed in the adult brain. We show that Tet1S is the predominantly expressed isoform, and is highly enriched in neurons, whereas Tet1FL is generally expressed at lower levels and more abundant in glia, suggesting their roles are at least partially cell-type specific. Using viral-mediated, isoform- and neuron-specific molecular tools, we find that Tet1S repression enhances, while Tet1FL impairs, hippocampal-dependent memory. In addition, the individual disruption of the two isoforms leads to contrasting changes in basal synaptic transmission and the dysregulation of unique gene ensembles in hippocampal neurons. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the mammalian brain.

scholarly journals Hydroxylation of 5-Methylcytosine by TET1 Promotes Active DNA Demethylation in the Adult Brain

Cell ◽  
2011 ◽  
Vol 145 (3) ◽  
pp. 423-434 ◽  
Author(s):  
Junjie U. Guo ◽  
Yijing Su ◽  
Chun Zhong ◽  
Guo-li Ming ◽  
Hongjun Song
Keyword(s):  
Dna Demethylation ◽  
Adult Brain ◽  
Active Dna Demethylation

scholarly journals Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stephanie Dobersch ◽  
Karla Rubio ◽  
Indrabahadur Singh ◽  
Stefan Günther ◽  
Johannes Graumann ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
High Mobility ◽  
Dna Demethylation ◽  
High Mobility Group ◽  
Regulation Of Transcription ◽  
Dna Breaks ◽  
Transcriptional Initiation ◽  
High Mobility Group Proteins ◽  
Active Dna Demethylation ◽  
Repair Mechanisms

AbstractIn addition to nucleosomes, chromatin contains non-histone chromatin-associated proteins, of which the high-mobility group proteins are the most abundant. Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. However, the order of events and the precise function of high-mobility group proteins during transcription initiation remain unclear. Here we show that high-mobility group AT-hook 2 protein (HMGA2) induces DNA nicks at the transcription start site, which are required by the histone chaperone FACT complex to incorporate nucleosomes containing the histone variant H2A.X. Further, phosphorylation of H2A.X at S139 (γ-H2AX) is required for repair-mediated DNA demethylation and transcription activation. The relevance of these findings is demonstrated within the context of TGFB1 signaling and idiopathic pulmonary fibrosis, suggesting therapies against this lethal disease. Our data support the concept that chromatin opening during transcriptional initiation involves intermediates with DNA breaks that subsequently require DNA repair mechanisms to ensure genome integrity.

scholarly journals Gene specific-loci quantitative and single-base resolution analysis of 5-formylcytosine by compound-mediated polymerase chain reaction

2018 ◽  
Vol 9 (15) ◽  
pp. 3723-3728 ◽  
Author(s):  
Yafen Wang ◽  
Chaoxing Liu ◽  
Xiong Zhang ◽  
Wei Yang ◽  
Fan Wu ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Dna Demethylation ◽  
Chain Reaction ◽  
Single Base ◽  
Active Dna Demethylation ◽  
Key Players ◽  
Resolution Analysis ◽  
Single Base Resolution ◽  
Polymerase Chain

5-Formylcytosine (5fC) is known as one of the key players in the process of active DNA demethylation and displays essential epigenetic functions in mammals.

scholarly journals Methyl-CpG-Binding Domain Protein MBD7 Is Required for Active DNA Demethylation in Arabidopsis

2015 ◽  
Vol 167 (3) ◽  
pp. 905-914 ◽  
Author(s):  
Chunlei Wang ◽  
Xiaomei Dong ◽  
Dan Jin ◽  
Yusheng Zhao ◽  
Shaojun Xie ◽  
...  
Keyword(s):  
Dna Demethylation ◽  
Binding Domain ◽  
Active Dna Demethylation ◽  
Domain Protein

scholarly journals SUMOylation coordinates BERosome assembly in active DNA demethylation during cell differentiation

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Roland Steinacher ◽  
Zeinab Barekati ◽  
Petar Botev ◽  
Anna Kuśnierczyk ◽  
Geir Slupphaug ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Dna Demethylation ◽  
Active Dna Demethylation

scholarly journals Cross-talk between active DNA demethylation, resetting of cellular metabolism and shoot apical growth in poplar bud break

2017 ◽  
Author(s):  
Daniel Conde ◽  
Mariano Perales ◽  
Anne-Laure Le Gac ◽  
Christopher Dervinis ◽  
Matias Kirst ◽  
...  
Keyword(s):  
Boreal Forests ◽  
Shoot Growth ◽  
Growth Cycle ◽  
Dna Demethylation ◽  
Bud Break ◽  
Winter Dormancy ◽  
Environmental Signals ◽  
Woody Perennials ◽  
Active Dna Demethylation ◽  
Dna Demethylase

AbstractAnnual dormancy-growth cycle is a developmental and physiological process essential for the survival of temperate and boreal forests. Seasonal control of shoot growth in woody perennials requires specific genetic programs integrated with the environmental signals. The environmental-controlled mechanisms that regulate the shift between winter dormancy to growth promoting genetic program are still unknown. Here, we show that dynamics in genomic DNA methylation (gDNA) levels regulate dormancy-growth cycle in poplar. We proved that the reactivation of cell division in the apical shoot that lead bud break process in spring, is preceded by a progressive reduction of gDNA methylation in apex tissue. We also identified that the induction in apex tissue of a chilling-dependent poplar DEMETER-LIKE 10 (PtaDML10) DNA demethylase precedes shoot growth reactivation. Transgenic poplars showing down-regulation of PtaDML8/10 caused delayed bud break. Genome wide transcriptome and methylome analysis and data mining revealed the gene targets of active DML-dependent DNA demethylation genetically associated to bud break. These data point to a chilling dependent-DEMETER-like DNA demethylase controlling the genetic shift from winter dormancy to a condition that promotes shoot apical vegetative growth in poplar.

scholarly journals Thymine DNA Glycosylase Can Rapidly Excise 5-Formylcytosine and 5-Carboxylcytosine

2011 ◽  
Vol 286 (41) ◽  
pp. 35334-35338 ◽  
Author(s):  
Atanu Maiti ◽  
Alexander C. Drohat
Keyword(s):  
Embryonic Development ◽  
Catalytic Mechanism ◽  
Excision Repair ◽  
Dna Demethylation ◽  
Oxidation Products ◽  
Dna Glycosylase ◽  
Thymine Dna Glycosylase ◽  
Active Demethylation ◽  
Active Dna Demethylation ◽  
Base Excision

Thymine DNA glycosylase (TDG) excises T from G·T mispairs and is thought to initiate base excision repair (BER) of deaminated 5-methylcytosine (mC). Recent studies show that TDG, including its glycosylase activity, is essential for active DNA demethylation and embryonic development. These and other findings suggest that active demethylation could involve mC deamination by a deaminase, giving a G·T mispair followed by TDG-initiated BER. An alternative proposal is that demethylation could involve iterative oxidation of mC to 5-hydroxymethylcytosine (hmC) and then to 5-formylcytosine (fC) and 5-carboxylcytosine (caC), mediated by a Tet (ten eleven translocation) enzyme, with conversion of caC to C by a putative decarboxylase. Our previous studies suggest that TDG could excise fC and caC from DNA, which could provide another potential demethylation mechanism. We show here that TDG rapidly removes fC, with higher activity than for G·T mispairs, and has substantial caC excision activity, yet it cannot remove hmC. TDG excision of fC and caC, oxidation products of mC, is consistent with its strong specificity for excising bases from a CpG context. Our findings reveal a remarkable new aspect of specificity for TDG, inform its catalytic mechanism, and suggest that TDG could protect against fC-induced mutagenesis. The results also suggest a new potential mechanism for active DNA demethylation, involving TDG excision of Tet-produced fC (or caC) and subsequent BER. Such a mechanism obviates the need for a decarboxylase and is consistent with findings that TDG glycosylase activity is essential for active demethylation and embryonic development, as are mechanisms involving TDG excision of deaminated mC or hmC.

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