What question did this study set out to answer?

To engineer a transient, hit-and-run epigenetic editing approach that establishes durable and inheritable gene silencing at endogenous loci in somatic cells.

September 1, 2016CellOpen Access

Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing

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Authors

AAAngelo AmabileThe San Raffaele Telethon Institute for Gene Therapy AMAlessandro MigliaraUniversity of California, San Francisco PCPaola CapassoHuman Technopole

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Implication

Experimental study demonstrates inheritable gene silencing in somatic and primary T cells, highlighting a durable hit-and-run epigenetic editing platform.

Key Points

To engineer a transient, hit-and-run epigenetic editing approach that establishes durable and inheritable gene silencing at endogenous loci in somatic cells.
Transiently delivered combinations of engineered transcriptional repressors inspired by embryonic stem cell retroviral silencing systems to target loci.
Assessed epigenetic persistence, genome-wide targeting specificity, resistance to cytokine activation, and reversibility via targeted DNA demethylation.
Evaluated the platform across multiple DNA-binding scaffolds, multiplexed gene targets, and diverse cell types, including primary human T lymphocytes.
Transient repressor exposure catalyzed de novo DNA methylation and repressive histone marks, maintaining long-term, inheritable silencing across cell divisions.
Silencing was sharply restricted to target loci without spreading to adjacent genes and resisted cytokine-mediated reactivation.
The repressive epigenetic state was reversible exclusively through targeted DNA demethylation and demonstrated broad portability across thousands of loci and primary T cells.

Cite This Study

Amabile et al. (2016) studied this question.

synapsesocial.com/papers/69d7d5a6a2a48916bbbee037 https://doi.org/10.1016/j.cell.2016.09.006

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Implication

Experimental study demonstrates inheritable gene silencing in somatic and primary T cells, highlighting a durable hit-and-run epigenetic editing platform.

Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing

Discussion

Member takes

Implication

Key Points

Cite This Study

Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing

Discussion

Member takes

Implication

Key Points

Cite This Study

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