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De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes
by
Shufaro, Yoel
, Deplus, Rachel
, Ueda, Jun
, Cedar, Howard
, Feldman, Nirit
, Shinkai, Yoichi
, Epsztejn-Litman, Silvina
, Abu-Remaileh, Monther
, Gerson, Ariela
, Fuks, François
, Bergman, Yehudit
in
Animals
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Cell Line
/ Deoxyribonucleic acid
/ DNA
/ DNA (Cytosine-5-)-Methyltransferases - genetics
/ DNA (Cytosine-5-)-Methyltransferases - metabolism
/ DNA Methylation
/ DNA Methyltransferase 3A
/ DNA Methyltransferase 3B
/ Embryo, Mammalian - physiology
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - physiology
/ Enzymes
/ Epigenesis, Genetic
/ Female
/ Gene Expression Profiling
/ Gene Expression Regulation, Developmental
/ Gene Silencing
/ Genetic regulation
/ Genetics
/ Histone Methyltransferases
/ Histone-Lysine N-Methyltransferase
/ Histones - metabolism
/ Humans
/ Life Sciences
/ Membrane Biology
/ Methyltransferases
/ Mice
/ Mice, Transgenic
/ Molecular biology
/ Molecular structure
/ Mutation
/ Octamer Transcription Factor-3 - genetics
/ Octamer Transcription Factor-3 - metabolism
/ Oligonucleotide Array Sequence Analysis
/ Physiological aspects
/ Properties
/ Protein Methyltransferases - metabolism
/ Protein Structure
/ Protein Structure, Tertiary
/ Stem cells
2008
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De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes
by
Shufaro, Yoel
, Deplus, Rachel
, Ueda, Jun
, Cedar, Howard
, Feldman, Nirit
, Shinkai, Yoichi
, Epsztejn-Litman, Silvina
, Abu-Remaileh, Monther
, Gerson, Ariela
, Fuks, François
, Bergman, Yehudit
in
Animals
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Cell Line
/ Deoxyribonucleic acid
/ DNA
/ DNA (Cytosine-5-)-Methyltransferases - genetics
/ DNA (Cytosine-5-)-Methyltransferases - metabolism
/ DNA Methylation
/ DNA Methyltransferase 3A
/ DNA Methyltransferase 3B
/ Embryo, Mammalian - physiology
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - physiology
/ Enzymes
/ Epigenesis, Genetic
/ Female
/ Gene Expression Profiling
/ Gene Expression Regulation, Developmental
/ Gene Silencing
/ Genetic regulation
/ Genetics
/ Histone Methyltransferases
/ Histone-Lysine N-Methyltransferase
/ Histones - metabolism
/ Humans
/ Life Sciences
/ Membrane Biology
/ Methyltransferases
/ Mice
/ Mice, Transgenic
/ Molecular biology
/ Molecular structure
/ Mutation
/ Octamer Transcription Factor-3 - genetics
/ Octamer Transcription Factor-3 - metabolism
/ Oligonucleotide Array Sequence Analysis
/ Physiological aspects
/ Properties
/ Protein Methyltransferases - metabolism
/ Protein Structure
/ Protein Structure, Tertiary
/ Stem cells
2008
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De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes
by
Shufaro, Yoel
, Deplus, Rachel
, Ueda, Jun
, Cedar, Howard
, Feldman, Nirit
, Shinkai, Yoichi
, Epsztejn-Litman, Silvina
, Abu-Remaileh, Monther
, Gerson, Ariela
, Fuks, François
, Bergman, Yehudit
in
Animals
/ Biochemistry
/ Biological Microscopy
/ Biomedical and Life Sciences
/ Cell Line
/ Deoxyribonucleic acid
/ DNA
/ DNA (Cytosine-5-)-Methyltransferases - genetics
/ DNA (Cytosine-5-)-Methyltransferases - metabolism
/ DNA Methylation
/ DNA Methyltransferase 3A
/ DNA Methyltransferase 3B
/ Embryo, Mammalian - physiology
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - physiology
/ Enzymes
/ Epigenesis, Genetic
/ Female
/ Gene Expression Profiling
/ Gene Expression Regulation, Developmental
/ Gene Silencing
/ Genetic regulation
/ Genetics
/ Histone Methyltransferases
/ Histone-Lysine N-Methyltransferase
/ Histones - metabolism
/ Humans
/ Life Sciences
/ Membrane Biology
/ Methyltransferases
/ Mice
/ Mice, Transgenic
/ Molecular biology
/ Molecular structure
/ Mutation
/ Octamer Transcription Factor-3 - genetics
/ Octamer Transcription Factor-3 - metabolism
/ Oligonucleotide Array Sequence Analysis
/ Physiological aspects
/ Properties
/ Protein Methyltransferases - metabolism
/ Protein Structure
/ Protein Structure, Tertiary
/ Stem cells
2008
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De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes
Journal Article
De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes
2008
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Overview
G9a is involved in gene silencing during early embryonic development, catalyzing the methylation of H3K9, which results in heterochromatinization, and also promoting methylation of DNA
de novo
. These two G9a activities are now dissected, and
de novo
DNA methylation is shown to occur via recruitment of Dnmt3a/3b and to be necessary and sufficient to prevent reprogramming.
The pluripotency-determining gene
Oct3/4
(also called
Pou5f1
) undergoes postimplantation silencing in a process mediated by the histone methyltransferase G9a. Microarray analysis now shows that this enzyme may operate as a master regulator that inactivates numerous early-embryonic genes by bringing about heterochromatinization of methylated histone H3K9 and
de novo
DNA methylation. Genetic studies in differentiating embryonic stem cells demonstrate that a point mutation in the G9a SET domain prevents heterochromatinization but still allows
de novo
methylation, whereas biochemical and functional studies indicate that G9a itself is capable of bringing about
de novo
methylation through its ankyrin domain, by recruiting Dnmt3a and Dnmt3b independently of its histone methyltransferase activity. These modifications seem to be programmed for carrying out two separate biological functions: histone methylation blocks target-gene reactivation in the absence of transcriptional repressors, whereas DNA methylation prevents reprogramming to the undifferentiated state.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ DNA
/ DNA (Cytosine-5-)-Methyltransferases - genetics
/ DNA (Cytosine-5-)-Methyltransferases - metabolism
/ Embryo, Mammalian - physiology
/ Embryonic Stem Cells - cytology
/ Embryonic Stem Cells - physiology
/ Enzymes
/ Female
/ Gene Expression Regulation, Developmental
/ Genetics
/ Histone-Lysine N-Methyltransferase
/ Humans
/ Mice
/ Mutation
/ Octamer Transcription Factor-3 - genetics
/ Octamer Transcription Factor-3 - metabolism
/ Oligonucleotide Array Sequence Analysis
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