Source 1primary paper2017Scientific Reports
Toolkit/CIB1-TALE fusion targeting Ascl1 promoter region
CIB1-TALE fusion targeting Ascl1 promoter region
Also known as: CIB1 fused to a Transcription Activator-Like Element (TALE)
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The CIB1-TALE fusion targeting the Ascl1 promoter is a locus-anchoring component of a blue-light-responsive epigenetic editing system. In combination with CRY2 fused to the catalytic domain of DNMT3A or TET1, it enables light-induced recruitment at the Ascl1 promoter and modulation of promoter methylation state and gene activity.
Usefulness & Problems
Why this is useful
This tool is useful for spatially and temporally controlled epigenetic manipulation at a defined endogenous promoter. The reported system uses blue light to selectively recruit methylation- or demethylation-associated catalytic activity to Ascl1, supporting optogenetic control of transcriptional regulation through promoter methylation editing.
Source:
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
Problem solved
It addresses the problem of achieving locus-specific and light-gated epigenetic editing at the Ascl1 promoter. The reported design couples sequence-specific promoter localization by a TALE with inducible CRY2/CIB1 association to control recruitment of DNMT3A-CD or TET1-CD.
Source:
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Techniques
Computational DesignTarget processes
editinglocalizationtranscriptionInput: Light
Implementation Constraints
The system is multi-component and requires a CIB1 fusion to a TALE that localizes to the Ascl1 promoter together with CRY2 fused to either DNMT3A catalytic domain or TET1 catalytic domain. Blue-light illumination was used to trigger co-localization, and the reported application was in neural stem cells.
The available evidence is limited to a single 2017 report describing the Ascl1-targeted system in neural stem cells. Quantitative performance metrics, off-target binding or editing data, reversibility, and validation across additional loci or cell types are not provided in the supplied evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity.
The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity.
The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity.
The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity.
The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity.
The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity.
The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity.
Optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site.
Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter.
Optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site.
Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter.
Optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site.
Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter.
Optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site.
Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter.
Optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site.
Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter.
Optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site.
Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter.
Optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site.
Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter.
The paper reports development of an optogenetic toolbox using CRY2/CIB1 fusions with DNMT3A-CD or TET1-CD and a TALE to enable locus-specific epigenetic editing at the Ascl1 promoter.
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
The paper reports development of an optogenetic toolbox using CRY2/CIB1 fusions with DNMT3A-CD or TET1-CD and a TALE to enable locus-specific epigenetic editing at the Ascl1 promoter.
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
The paper reports development of an optogenetic toolbox using CRY2/CIB1 fusions with DNMT3A-CD or TET1-CD and a TALE to enable locus-specific epigenetic editing at the Ascl1 promoter.
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
The paper reports development of an optogenetic toolbox using CRY2/CIB1 fusions with DNMT3A-CD or TET1-CD and a TALE to enable locus-specific epigenetic editing at the Ascl1 promoter.
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
The paper reports development of an optogenetic toolbox using CRY2/CIB1 fusions with DNMT3A-CD or TET1-CD and a TALE to enable locus-specific epigenetic editing at the Ascl1 promoter.
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
The paper reports development of an optogenetic toolbox using CRY2/CIB1 fusions with DNMT3A-CD or TET1-CD and a TALE to enable locus-specific epigenetic editing at the Ascl1 promoter.
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
The paper reports development of an optogenetic toolbox using CRY2/CIB1 fusions with DNMT3A-CD or TET1-CD and a TALE to enable locus-specific epigenetic editing at the Ascl1 promoter.
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
Approval Evidence
1 source3 linked approval claimsfirst-pass slug cib1-tale-fusion-targeting-ascl1-promoter-region
Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
Source:
epigenetic editing effectsupports
The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
We found that this spatiotemporal association of the fusion proteins selectively alters the methylation state and also regulates gene activity.
Source:
light induced colocalizationsupports
Optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site.
Optimized blue-light illumination triggered the co-localization of TALE constructs with DNMT3A-CD or TET1-CD fusion proteins at the targeted site of the Ascl1 promoter.
Source:
tool developmentsupports
The paper reports development of an optogenetic toolbox using CRY2/CIB1 fusions with DNMT3A-CD or TET1-CD and a TALE to enable locus-specific epigenetic editing at the Ascl1 promoter.
Herein, we have developed an optogenetic toolbox fused to the catalytic domain (CD) of DNA-methyltransferase3A (DNMT3A-CD) or Ten-Eleven Dioxygenase-1 (TET1-CD) for loci-specific alteration of the methylation state at the promoter of Ascl1 (Mash1). Optogenetical protein pairs, CRY2 linked to DNMT3A-CD or TET1-CD and CIB1 fused to a Transcription Activator-Like Element (TALE) locating an Ascl1 promoter region, were designed for site specific epigenetic editing.
Source:
Comparisons
Source-backed strengths
Source literature reports that optimized blue-light illumination triggered co-localization of the TALE construct with DNMT3A-CD or TET1-CD fusion proteins at the targeted Ascl1 promoter site. The spatiotemporal association of the fusion proteins selectively altered methylation state and regulated gene activity at the Ascl1 promoter.
Ranked Citations
- 1.