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Series GSE219080 Query DataSets for GSE219080
Status Public on May 17, 2024
Title Epigenetic regulation by dynamic RNA G-quadruplex folding and unfolding (CHART-Seq)
Organism Mus musculus
Experiment type Other
Summary Whether RNA G-quadruplexes (rG4) form extensively in vivo and what roles they play remain actively debated. Among their proposed functions is recognition of Polycomb repressive complex 2 (PRC2), but how the interaction results in epigenetic regulation is not understood. Here we demonstrate that rG4s form dynamically during ES cell differentiation and require ATRX’s helicase function to unwind competing secondary structures. Mutating ATRX causes rG4 depletion on a transcriptome-wide basis and dramatically increases gene expression. We identify and mutate rG4s within Xist RNA and mechanistically separate PRC2’s recruitment versus catalysis. Surprisingly, although rG4s recruit PRC2, unfolding the rG4 structure causes PRC2 hyperactivation, entrapment of PRC2 in the S1 chromosomal compartment, and loss of gene silencing. Thus, we link dynamic rG4 folding and unfolding to PRC2 recruitment, trans-compartmental Xist migration, regulated activation of PRC2, and whole-chromosome gene silencing.
 
Overall design Modified existing rG4-seq and RT-Stop protocols were performed and generated an “in vitro” and “in vivo” pipeline, based on differential sensitivity of various RNA structures to dimethyl sulfate (DMS), reverse transcriptase (RT), and the monovalent cations Li+ versus K+.
Web link https://doi.org/10.1016/j.molcel.2024.04.015
 
Contributor(s) Lee YW, Weissbein U, Blum R, Lee JT
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Nov 30, 2022
Last update date May 18, 2024
Contact name yongwoo lee
E-mail(s) ylee@molbio.mgh.harvard.edu
Phone 6177552856
Organization name MASSACHUSETTS GENERAL HOSPITAL
Department Mol bio
Lab Jeannie Lee Lab
Street address 185 Cambridge St
City Boston
State/province MA
ZIP/Postal code 02114
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM7946789 WT_D7_Xist_CHART rep1
GSM7946790 3rG4_cl5_D7_Xist_CHART rep1
GSM7946791 3rG4_cl6_D7_Xist_CHART rep1
This SubSeries is part of SuperSeries:
GSE219083 G-quadruplex folding in Xist RNA antagonizes PRC2 activity for step-wise regulation of X-chromosome inactivation
Relations
BioProject PRJNA907001

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE219080_RAW.tar 1.3 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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