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Series GSE183934 Query DataSets for GSE183934
Status Public on Jun 16, 2024
Title Perturbation of TET2 condensation induces genome-wide promiscuous DNA hypomethylation and curtails leukemia cell growth
Organisms Homo sapiens; Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary The Ten-Eleven Translocation (TET)-mediated DNA modification pathway is intimately involved in transcriptional regulation. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine (5hmC) is enriched at selected enhancers in a tissue specific manner, with the underlying mechanism yet to be clarified. Here, we report a low complexity insert (LCI) domain within the TET2 catalytic domain that facilitates TET2 condensation and enables its precise chromatin binding, which leads to DNA demethylation at specific genomic regions. Perturbation of TET2 condensation results in promiscuous DNA demethylation that accounts for large-scale topological changes in the genome, which alter the expression of genes that associated with patient survival and ultimately suppresses leukemia cell growth both in vitro and in vivo. Our study illuminates a previously neglected liquid-like condensation property of TET2 in gene regulation and explores the potential of targeting biomolecular condensation of epigenetic enzymes for effective cancer intervention.
 
Overall design Comparative gene expression profiling analysis of RNA-seq data for MOLM13 cells expressing human TET2 CD and TET2-CDΔLCI .DNA from mESC or MOLM13 cells expressing TET2-CD and TET2-CDΔLCI were extracted and subjected to WGBS. We generated mouse embryonic stem cells (mESCs) that stably expressed DamID only, TET2CD-Dam or TET2CDΔLCI-Dam. DNA from mESC or MOLM13 cells expressing TET2-CD and TET2-CDΔLCI were extracted and subjected to CMS-IP. Mouse stem cells (mESCs) 5hmC mapping (CMSIP).
 
Contributor(s) Guo L, Li J, Hu X, Lee Y, Pan G, Zhou Y, Davis P, Goodell MA, Huang Y
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Submission date Sep 10, 2021
Last update date Jun 17, 2024
Contact name Jia Li
E-mail(s) jiali@tamu.edu
Organization name Texas A&M U Health Science Center
Department CEDP
Lab Jia Li Lab
Street address 2121 W HOLCOMBE BLVD
City Houston
State/province Texas
ZIP/Postal code 77030
Country USA
 
Platforms (4)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (50)
GSM5574528 5hmC of Tet1/2/3 triple KO mESC transfected with human Tet2 CD domain rep1
GSM5574529 5hmC of Tet1/2/3 triple KO mESC transfected with human Tet2 CD domain rep2
GSM5574530 5hmC of Tet1/2/3 triple KO mESC transfected with human Tet2 CD domain rep3
Relations
BioProject PRJNA762355
SRA SRP336573

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Supplementary file Size Download File type/resource
GSE183934_MOLM13_mrg.counts2.normalize.txt.gz 1.0 Mb (ftp)(http) TXT
GSE183934_RAW.tar 27.2 Gb (http)(custom) TAR (of BW, HIC)
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record
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