GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE141683 Query DataSets for GSE141683
Status Public on Mar 30, 2022
Title Targeting Xist with compounds that disrupt RNA structure and X-inactivation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Although >98% of our genome is noncoding, nearly all drugs on the market target one of ~700 disease-related proteins. The historical reluctance to invest in noncoding RNA stems partly from requirements for drug targets to adopt a single stable conformation. Most RNAs can adopt several conformations of similar stabilities. RNA structures also remain challenging to determine. Nonetheless, an increasing number of diseases is now being attributed to noncoding RNA and the ability to target them would vastly expand the chemical space for drug development. Here we devise a screening strategy and identify small molecules that hit the non-coding RNA prototype, Xist. The X1 compound has drug-like properties and binds specifically to Xist’s RepA motif in vitro and in vivo. SAXS analysis reveals that RepA can adopt multiple conformations but favors one structure in solution. X1 binding reduces RepA’s conformational space, displaces cognate interacting protein factors (PRC2, SPEN), suppresses H3K27 trimethylation, and blocks initiation of X-inactivation. X1 inhibits cell differentiation and growth in a female-specific manner. Thus, RNA can be systematically targeted by drug-like compounds that disrupt RNA structure and epigenetic function.
Overall design Day 5 TST cells are subjected to drug or control and then used in three deep sequencing analyses, RNA sequencing, H3K27me3 ChIP, and Suz12 ChIP.

Please note that RAb5-*.div.RAb5-*bw files were generated from both input and ChIP samples, and are linked to the corresponding ChIP-Suz12* sample records.
Web link
Contributor(s) Aguilar  R, Spencer KB, Kesner  B, Rizvi NF, Badmalia MD, Mrozowich T, Mortison JD, Rivera C, Smith GF, Burchard J, Dandliker P, Patel TR, Nickbarg  EB, Lee JT
Citation(s) 35355011
Submission date Dec 09, 2019
Last update date Apr 22, 2022
Contact name barry A kesner
Phone 6175197106
Organization name molecular biology
Street address 49 charlemont street
City newton
State/province ma
ZIP/Postal code 02461
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (12)
GSM4211083 ChIP-input-DMSO_1 [RAb3-1]
GSM4211084 ChiP-H3K27me3  [RAb3-2]
GSM4211085 ChIP-input_X1treated_1 [RAb3-3]
BioProject PRJNA594367
SRA SRP235281

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
GSE141683_DeSeq.RA4.cas.treated.rel.dmso.txt.gz 8.1 Kb (ftp)(http) TXT
GSE141683_DeSeq.RA4.mus.treatd.rel.dmso.txt.gz 564.6 Kb (ftp)(http) TXT
GSE141683_RA3_raw_counts.txt.gz 1.6 Mb (ftp)(http) TXT
GSE141683_RA4.raw.counts.txt.gz 684.5 Kb (ftp)(http) TXT
GSE141683_RA5_raw_counts.txt.gz 1.6 Mb (ftp)(http) TXT
GSE141683_RAW.tar 85.2 Gb (http)(custom) TAR (of BW) 540.9 Mb (ftp)(http) BW 543.1 Mb (ftp)(http) BW 540.7 Mb (ftp)(http) BW 541.2 Mb (ftp)(http) BW 541.4 Mb (ftp)(http) BW 540.4 Mb (ftp)(http) BW
GSE141683_RAb4.AnalyzeRepeats.fpkm_gt_1.genes_pm3000.chr13.comp.bed.gz 3.5 Kb (ftp)(http) BED
GSE141683_RAb4.AnalyzeRepeats.fpkm_gt_1.genes_pm3000.chrX.comp.bed.gz 4.1 Kb (ftp)(http) BED
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap