GSE214547 Multiplex Epigenome Editing of MECP2 to Rescue Rett Syndrome Neurons (ChIP-Seq)

Contributors : Xiaonan Guan ; Rudolf Jaenisch ; X S LiuSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensRett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by loss-of-function heterozygous mutations of MECP2. Reactivation of the silent wild-type MECP2 allele on the inactive X chromosome (Xi) represents a promising therapeutic opportunity for female RTT patients. Here, we applied a multiplex epigenome editing approach to reactivate MECP2 on Xi. Demethylation of the MECP2 promoter by dCas9-Tet1 with target sgRNA reactivated MECP2 on Xi in RTT hESCs without detectable off-target effects at the transcriptome level. Neurons derived from methylation edited RTT hESCs reversed the smaller soma size and electrophysiological abnormalities. Insulation of the methylation edited MECP2 locus in RTT neurons by dCpf1-CTCF with target crRNA stabilized MECP2 reactivation and rescued the RTT-related neuronal defects, providing a proof-of-concept study for multiplex epigenome editing to treat RTT.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research