Epigenetic CRISPR/Cas9

Epigenetic CRISPR/Cas9

Epigenetic CRISPR/Cas9 is a modified form of the gene editing technology CRISPR, designed to modify the epigenome, rather than the genome. Without cutting DNA the system activates or represses genes.

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Epigenetic CRISPR-Cas9 is a modified form of the genome editing platform CRISPR-Cas9 that does not cut DNA but affects gene expression levels. Gene expression levels depend on DNA methylation levels and whether chromatin conformation is in an active or repressed state. Epigenetic CRISPR-Cas9 uses the nuclease dead Cas9 (dCas9) to target the genome and instead of altering the genetic sequence, the system alters the epigenome by bringing transcriptional activators, repressors and chromatin modifiers to the desired genomic region. This technique allows researchers to study how epigenetic marks like DNA methylation, histone acetylationacetylation and chromatin modifier proteins affect gene expression in cultured mammalian cells and live mice . Programmable gene regulation via Epigenetic CRISPR-Cas9 has potential clinical applications .

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Hypermethylation and inactivity of the FMR1FMR1 gene is responsible for Fragile X Syndrome, the most common form of intellectual disability in males. Rudolph Jaenisch’s group at the Whitehead Institute for Biomedical Research, Cambridge, developed a version of dCas9-Tet1 which they used to activate FMR1 in induced pluripotent stem cells (iPSCs) from patients with Fragile X Syndrome . When the iPSCs with reactivated FMR1 were differentiated into neurons, neural function was rescued and remained rescued after transplant into mouse brain. Jaenisch’s group also showed that they could also use their system to activate FMR1 in post-mitotic neurons.

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Juan Carlos Izpisua BelmonteJuan Carlos Izpisua Belmonte of the Salk Institute for Biological Studies, California and his team designed guide RNAs to bring transcriptional activators with dCas9 to activate genes of interest . Instead of fixing the mutated gene in a disease, their approach is to upregulate other genes in the disease pathway that can compensate for the malfunctioning gene. In mouse models for kidney disease and muscular dystrophy their approach improved kidney and muscle function.

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Epigenetic CRISPR-Cas9 is a modified form of the genome editing platform CRISPR-Cas9 that does not cut DNA but affects gene expression levels. Gene expression levels depend on DNA methylationDNA methylation levels and whether chromatin conformation is in an active or repressed state. Epigenetic CRISPR-Cas9 uses the nuclease dead Cas9 (dCas9) to target the genome and instead of altering the genetic sequence, the system alters the epigenome by bringing transcriptional activators, repressors and chromatin modifiers to the desired genomic region. This technique allows researchers to study how epigenetic marks like DNA methylation, histone acetylation and chromatin modifier proteins affect gene expression in cultured mammalian cells and live mice . Programmable gene regulation via Epigenetic CRISPR-Cas9 has potential clinical applications .

Jude Gomila
Jude Gomila approved a suggestion from Golden's AI on 31 Aug, 2018
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Juan Carlos Izpisua Belmonte of the Salk Institute for Biological Studies, CaliforniaCalifornia and his team designed guide RNAs to bring transcriptional activators with dCas9 to activate genes of interest . Instead of fixing the mutated gene in a disease, their approach is to upregulate other genes in the disease pathway that can compensate for the malfunctioning gene. In mouse models for kidney disease and muscular dystrophy their approach improved kidney and muscle function.

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Jude Gomila approved a suggestion from Golden's AI on 29 Aug, 2018
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Acetylation modifications to histones, the proteins, which package DNA into chromatin change the conformation of the chromatin. Charles Gersbach and Timothy Reddy at Duke UniversityDuke University, fused human acetyltransferase, p300 to dCas9. The fusion protein causes histone H3 lysine 27 to become acetylated at target sites, which activated target genes .

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Epigenetic CRISPR/Cas9

Gene editing technology

Epigenetic CRISPR/Cas9 is a modified form of the gene editing technology CRISPR, designed to modify the epigenome, rather than the genome. Without cutting DNA the system activates or represses genes.

Article

Epigenetic CRISPR/Cas9 is a modified form of the gene editing technology CRISPR, designed to activate genes without cutting DNA by adding or removing methyl groups in specific positions.

Epigenetic CRISPR-Cas9 is a modified form of the genome editing platform CRISPR-Cas9 that does not cut DNA but affects gene expression levels. Gene expression levels depend on DNA methylation levels and whether chromatin conformation is in an active or repressed state. Epigenetic CRISPR-Cas9 uses the nuclease dead Cas9 (dCas9) to target the genome and instead of altering the genetic sequence, the system alters the epigenome by bringing transcriptional activators, repressors and chromatin modifiers to the desired genomic region. This technique allows researchers to study how epigenetic marks like DNA methylation, histone acetylation and chromatin modifier proteins affect gene expression in cultured mammalian cells and live mice . Programmable gene regulation via Epigenetic CRISPR-Cas9 has potential clinical applications .

...

This technique allows researchers to see how changes affect gene expression and has been tested in cultured mouse cells and live mice.

Turning up gene expression

Juan Carlos Izpisua Belmonte of the Salk Institute for Biological Studies, California and his team designed guide RNAs to bring transcriptional activators with dCas9 to activate genes of interest . Instead of fixing the mutated gene in a disease, their approach is to upregulate other genes in the disease pathway that can compensate for the malfunctioning gene. In mouse models for kidney disease and muscular dystrophy their approach improved kidney and muscle function.

Acetylation modifications to histones, the proteins, which package DNA into chromatin change the conformation of the chromatin. Charles Gersbach and Timothy Reddy at Duke University, fused human acetyltransferase, p300 to dCas9. The fusion protein causes histone H3 lysine 27 to become acetylated at target sites, which activated target genes .

DNA methylation is a modification to DNA which regulates the expression of genes. Ronggui Hu’s lab at the Shanghai Institutes for Biological Sciences developed an epigenetic CRISPR-Cas9 system that includes the CpG demethylase enzyme, Tet1 to demethylate the promoter regions of target genes .

Hypermethylation and inactivity of the FMR1 gene is responsible for Fragile X Syndrome, the most common form of intellectual disability in males. Rudolph Jaenisch’s group at the Whitehead Institute for Biomedical Research, Cambridge, developed a version of dCas9-Tet1 which they used to activate FMR1 in induced pluripotent stem cells (iPSCs) from patients with Fragile X Syndrome . When the iPSCs with reactivated FMR1 were differentiated into neurons, neural function was rescued and remained rescued after transplant into mouse brain. Jaenisch’s group also showed that they could also use their system to activate FMR1 in post-mitotic neurons.

Turning down gene expression

Facioscapulohumeral (FSH) Muscular Dystrophy is an epigenetic disease. Abnormal chromatin structure leads to aberrant activation of DUX4-FL, which is normally repressed, leads to disease pathology. Peter L. Jones and his team, now at University of Nevada used dCas9 fused to the KRAB repressor to silence DUX4-FL in muscle cell lines . A method of turning down gene expression by fusing dCas9 with DNA methyltransferase Dnmt3a, which adds methyl groups to target regions of DNA was described by Rudolph Jaenisch’s group .

Further reading

Title
Author
Link
Type

CRISPR-Cas9 genomeScalpel editingor inducesStraitjacket: aCRISPR/Cas9 p53-mediatedApproaches DNAfor damageMuscular responseDystrophies

Jussi Taipale,Charis SandeepL. BotlaHimeda, EmmaTakako HaapaniemiI. Jones, Bernhardand Schmierer,Peter JennaL. PerssonJones

Documentaries, videos and podcasts

Title
Date
Link

Salk scientists modify CRISPR to epigenetically treat diabetes, kidney disease, muscular dystrophy

Dec 7, 2017

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Author
Title
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Jussi Taipale, Sandeep Botla, Emma Haapaniemi, Bernhard Schmierer, Jenna Persson

CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response

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Author
Title
Link
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Hsin-Kai Liao7, Fumiyuki Hatanaka7, Toshikazu Araoka7, Pradeep Reddy, Min-Zu Wu, Yinghui Sui, Takayoshi Yamauchi, Masahiro Sakurai, David D. O’Keefe, Estrella Núñez-Delicado, Pedro Guillen, Josep M. Campistol, Cheng-Jang Wu, Li-Fan Lu, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte

In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

http://www.cell.com/cell/abstract/S0092-8674(17)31247-3http://www.cell.com/cell/abstract/S0092-8674(17)31247-3

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This technique allows researchers to see how changes affect gene expressiongene expression and has been tested in cultured mouse cells and live mice.

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Tianchang He
Tianchang He edited on 5 Jun, 2018
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Further reading (+5/-5 characters)
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Author
Title
Link
Type

Hsin-Kai Liao7, Fumiyuki Hatanaka7, Toshikazu Araoka7, Pradeep Reddy, Min-Zu Wu, Yinghui Sui, Takayoshi Yamauchi, Masahiro Sakurai, David D. O’Keefe, Estrella Núñez-Delicado, Pedro Guillen, Josep M. Campistol, Cheng-Jang Wu, Li-Fan Lu, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte

In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

http://www.cell.com/cell/abstract/S0092-8674(17)31247-3

Academic Paperpaper

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Academic papers (-1 rows) (-3 cells) (-432 characters)
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Academic papers

Author
Title
Link

Hsin-Kai Liao7, Fumiyuki Hatanaka7, Toshikazu Araoka7, Pradeep Reddy, Min-Zu Wu, Yinghui Sui, Takayoshi Yamauchi, Masahiro Sakurai, David D. O’Keefe, Estrella Núñez-Delicado, Pedro Guillen, Josep M. Campistol, Cheng-Jang Wu, Li-Fan Lu, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte

In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

http://www.cell.com/cell/abstract/S0092-8674(17)31247-3

Further reading

Author
Title
Link
Type

Hsin-Kai Liao7, Fumiyuki Hatanaka7, Toshikazu Araoka7, Pradeep Reddy, Min-Zu Wu, Yinghui Sui, Takayoshi Yamauchi, Masahiro Sakurai, David D. O’Keefe, Estrella Núñez-Delicado, Pedro Guillen, Josep M. Campistol, Cheng-Jang Wu, Li-Fan Lu, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte

In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

http://www.cell.com/cell/abstract/S0092-8674(17)31247-3

Academic Paper

Edits on 21 Dec, 2017
Jude Gomila
Jude Gomila edited on 21 Dec, 2017
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Article

Epigenetic CRISPR/Cas9 is a modified form of the gene editing technology CRISPRCRISPR, designed to activate genes without cutting DNA by adding or removing methyl groups in specific positions.

Jude Gomila
Jude Gomila edited on 21 Dec, 2017
Edits made to:
Article (+193 characters)
Topic thumbnail

Epigenetic CRISPR/Cas9

Epigenetic CRISPR/Cas9 is a modified form of the gene editing technology CRISPR, designed to modify the epigenome, rather than the genome. Without cutting DNA the system activates or represses genes.

Article

Epigenetic CRISPR/Cas9 is a modified form of the gene editing technology CRISPR, designed to activate genes without cutting DNA by adding or removing methyl groups in specific positions.

This technique allows researchers to see how changes affect gene expression and has been tested in cultured mouse cells and live mice.

Edits on 14 Dec, 2017
Rachel Phythian"New topic"
Rachel Phythian edited on 14 Dec, 2017
Edits made to:
Description (+23 characters)
Academic papers (+1 rows)
Related Topics (+3 topics)
Topic thumbnail

Epigenetic CRISPR/Cas9

Gene editing technology

Article

Epigenetic CRISPR/Cas9 is a modified form of the gene editing technology CRISPR, designed to activate genes without cutting DNA.

Academic papers

Author
Title
Link

Hsin-Kai Liao7, Fumiyuki Hatanaka7, Toshikazu Araoka7, Pradeep Reddy, Min-Zu Wu, Yinghui Sui, Takayoshi Yamauchi, Masahiro Sakurai, David D. O’Keefe, Estrella Núñez-Delicado, Pedro Guillen, Josep M. Campistol, Cheng-Jang Wu, Li-Fan Lu, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte

In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

http://www.cell.com/cell/abstract/S0092-8674(17)31247-3

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Rachel Phythian created this topic on 14 Dec, 2017
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 Epigenetic CRISPR/Cas9

Epigenetic CRISPR/Cas9 is a modified form of the gene editing technology CRISPR, designed to modify the epigenome, rather than the genome. Without cutting DNA the system activates or represses genes.

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