Perspectives for epigenetic editing in crops

Scleroderma or systemic sclerosis is thought to result from the interplay between environmental or non-genetic factors in a genetically susceptible individual. Epigenetic modifications are influenced by genetic variation and environmental exposures, and change with chronological age and between populations. Despite progress in identifying genetic, epigenetic, and environmental risk factors, the underlying mechanism of systemic sclerosis remains unclear. Since epigenetics provides the regulatory mechanism linking genetic and non-genetic factors to gene expression, understanding the role of epigenetic regulation in systemic sclerosis will elucidate how these factors interact to cause systemic sclerosis. Among the cell types under tight epigenetic control and susceptible to epigenetic dysregulation, immune cells are critically involved in early pathogenic events in the progression of fibrosis and systemic sclerosis. This review starts by summarizing the changes in DNA methylation, histone modification, and non-coding RNAs associated with systemic sclerosis. It then discusses the role of genetic, ethnic, age, and environmental effects on epigenetic regulation, with a focus on immune system dysregulation. Given the potential of epigenome editing technologies for cell reprogramming and as a therapeutic approach for durable gene regulation, this review concludes with a prospect on epigenetic editing. Although epigenomics in systemic sclerosis is in its infancy, future studies will help elucidate the regulatory mechanisms underpinning systemic sclerosis and inform the design of targeted epigenetic therapies to control its dysregulation.

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Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer’s disease mice

Brain ◽

10.1093/brain/awx272 ◽

2017 ◽

Vol 140 (12) ◽

pp. 3252-3268 ◽

Cited By ~ 44

Author(s):

Fernando J Bustos ◽

Estibaliz Ampuero ◽

Nur Jury ◽

Rodrigo Aguilar ◽

Fahimeh Falahi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Epigenetic Editing

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CRISPR-Based Targeted Epigenetic Editing Enables Gene Expression Modulation of the Silenced Beta-Galactoside Alpha-2,6-Sialyltransferase 1 in CHO Cells

Biotechnology Journal ◽

10.1002/biot.201700217 ◽

2018 ◽

Vol 13 (10) ◽

pp. 1700217 ◽

Cited By ~ 18

Author(s):

Nicolas Marx ◽

Clemens Grünwald-Gruber ◽

Nina Bydlinski ◽

Heena Dhiman ◽

Ly Ngoc Nguyen ◽

...

Keyword(s):

Gene Expression ◽

Cho Cells ◽

Expression Modulation ◽

Epigenetic Editing

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F165. Using CRISPR/Cas9-Based Epigenetic Editing to Study the Role of Schizophrenia-Related Alterations in DNA Methylation on Dendritic Spine Density

Biological Psychiatry ◽

10.1016/j.biopsych.2019.03.702 ◽

2019 ◽

Vol 85 (10) ◽

pp. S277

Author(s):

Jennifer Kuflewski ◽

Christopher Hensler ◽

Shahwar Tariq ◽

David Lewis ◽

Robert Sweet ◽

...

Keyword(s):

Dna Methylation ◽

Dendritic Spine ◽

Spine Density ◽

Dendritic Spine Density ◽

Epigenetic Editing

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In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene

Nature Communications ◽

10.1038/s41467-019-12013-y ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 5

Author(s):

Cyril J. Peter ◽

Atsushi Saito ◽

Yuto Hasegawa ◽

Yuya Tanaka ◽

Mohika Nagpal ◽

...

Keyword(s):

Therapeutic Potential ◽

Gene Promoters ◽

Risk Genes ◽

Risk Gene ◽

Axonal Development ◽

Repressor Proteins ◽

Repressor Complex ◽

Genes Encoding ◽

Epigenetic Editing

Abstract Many neuropsychiatric risk genes contribute to epigenetic regulation but little is known about specific chromatin-associated mechanisms governing the formation of neuronal connectivity. Here we show that transcallosal connectivity is critically dependent on C11orf46, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus. C11orf46 haploinsufficiency was associated with hypoplasia of the corpus callosum. C11orf46 knockdown disrupted transcallosal projections and was rescued by wild type C11orf46 but not the C11orf46R236H mutant associated with intellectual disability. Multiple genes encoding key regulators of axonal development, including Sema6a, were hyperexpressed in C11orf46-knockdown neurons. RNA-guided epigenetic editing of Sema6a gene promoters via a dCas9-SunTag system with C11orf46 binding normalized SEMA6A expression and rescued transcallosal dysconnectivity via repressive chromatin remodeling by the SETDB1 repressor complex. Our study demonstrates that interhemispheric communication is sensitive to locus-specific remodeling of neuronal chromatin, revealing the therapeutic potential for shaping the brain’s connectome via gene-targeted designer activators and repressor proteins.

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From the pathophysiology of the human lung alveolus to epigenetic editing: Congress 2018 highlights from ERS Assembly 3 “Basic and Translational Science.”

ERJ Open Research ◽

10.1183/23120541.00194-2018 ◽

2019 ◽

Vol 5 (2) ◽

pp. 00194-2018 ◽

Cited By ~ 1

Author(s):

Marko Z. Nikolić ◽

Eva M. Garrido-Martin ◽

Flavia R. Greiffo ◽

Aurélie Fabre ◽

Irene H. Heijink ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Human Lung ◽

Basic Research ◽

Clinical Findings ◽

Translational Science ◽

European Respiratory Society ◽

Lung Alveolus ◽

Epigenetic Editing ◽

Selection Of ◽

Novel Therapeutic

The European Respiratory Society (ERS) International Congress is the largest respiratory congress and brings together leading experts in all fields of respiratory medicine and research. ERS Assembly 3 shapes the basic and translational science aspects of this congress, aiming to combine cutting-edge novel developments in basic research with novel clinical findings. In this article, we summarise a selection of the scientific highlights from the perspective of the three groups within Assembly 3. In particular, we discuss new insights into the pathophysiology of the human alveolus, novel tools in organoid development and (epi)genome editing, as well as insights from the presented abstracts on novel therapeutic targets being identified for idiopathic pulmonary fibrosis.

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Epigenetic Inheritance is Gated by Naive Pluripotency and Dppa2

10.1101/2021.05.11.443595 ◽

2021 ◽

Author(s):

Valentina Carlini ◽

Cristina Policarpi ◽

Jamie A Hackett

Keyword(s):

De Novo ◽

Epigenetic Inheritance ◽

Developmental Model ◽

Lineage Specification ◽

Chromatin States ◽

Genome Wide ◽

Mechanistic Basis ◽

Endogenous Loci ◽

Epigenetic Editing

Environmental factors can trigger cellular responses that propagate across mitosis or even generations. Perturbations to the epigenome could underpin such acquired changes, however, the extent and contexts in which modified chromatin states confer heritable memory in mammals is unclear. Here we exploit a modular epigenetic editing strategy to establish de novo heterochromatin domains (epialleles) at endogenous loci and track their inheritance in a developmental model. We find that naive pluripotent phases systematically erase ectopic domains of heterochromatin via active mechanisms, which acts as an intergenerational safeguard against transmission of epialleles. Upon lineage specification however, acquired chromatin states can be probabilistically inherited under selectively favourable conditions, including propagation of p53 silencing through in vivo development. Using genome-wide CRISPR screening, we identify the mechanisms that block heritable silencing memory in pluripotent cells, and demonstrate removal of Dppa2 unlocks the potential for epigenetic inheritance uncoupled from DNA sequence. Our study outlines a mechanistic basis for how epigenetic inheritance is restricted in mammals, and reveals genomic- and developmental- contexts in which heritable memory is feasible.

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