GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE135320 Query DataSets for GSE135320
Status Public on Apr 06, 2020
Title Alteration of CTCF associated chromatin neighborhood inhibits TAL1-driven oncogenic transcription program and leukemogenesis
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Aberrant activation of the TAL1 oncogene is associated with up to 60% of T-ALL patients and is involved in CTCF mediated genome organization within the TAL1 locus, suggesting the importance of the CTCF boundary in the molecular pathogenesis of T-ALL. Here, we show that deletion of CTCF binding site (CBS) or alternation of CTCF boundary orientation alters expression of the TAL1 oncogene in a cell context dependent manner. Deletion of the CTCF binding site located at -31 Kb upstream of TAL1 (-31CBS) reduces chromatin accessibility in the +51 enhancer and the TAL1 promoter I, and blocks long-range interaction between the +51 erythroid enhancer and TAL1 promoter 1b that inhibits expression of TAL1 in erythroid cells, but not in T-ALL cells. However, in the TAL1 expressed T-ALL primary patient samples or cell line, the T-ALL prone TAL1 promoter IV specifically interacts with the +19 stem cell enhancer that is located 19 kb downstream of the TAL1 promoter and required for TAL1 transcription in the hematopoietic stem cell (HSC) stage. Inversion of -31CBS orientation, but not deletion of -31CBS, alters chromatin accessibility, enhancer/promoter histone modifications, CTCF-mediated topological associated domain (TAD), and enhancer/promoter interaction in the TAL1 locus leading to inhibition of TAL1 oncogene expression and TAL1-driven T cell leukemogenesis. Thus, our data reveal that the TAL1 +19 stem cell enhancer acts not only as stem cell enhancer, but also as a leukemia specific enhancer to activate the TAL1 oncogene in T-ALL. Manipulation of CTCF defined chromatin boundary can alter TAL1 TAD and oncogenic transcription networks in leukemogenesis.
Overall design We have finished the RNA-SEQ, ATAC-seq, ChIP-seq and HiC-seq to investigate the role of TAL1 transcription and CTCF boundaries in leukemogenesis. Jurkat leukemia cells and K562 cells were used to perform the RNA-seq, ATAC-seq, 4Cseq, CHIP-seq and HiC-seq analysis.
Contributor(s) Luo H, Huang S
Citation(s) 32086528
Submission date Aug 02, 2019
Last update date Apr 06, 2020
Contact name Suming Huang
Organization name Penn State University
Department Pediatrics
Street address 500 University Dr.
City Hershey
State/province PA
ZIP/Postal code 17033
Country USA
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (24)
GSM4005268 31CBS-WT-Jurkat-RNA-seq-1
GSM4005269 31CBS-WT-Jurkat-RNA-seq-2
GSM4005270 31CBS-inv-Jurkat-RNA-seq-1
BioProject PRJNA558386
SRA SRP217227

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
GSE135320_RAW.tar 3.9 Mb (http)(custom) TAR (of BED, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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