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Series GSE114981 Query DataSets for GSE114981
Status Public on Dec 03, 2019
Title Activation of HOTTIP lncRNA perturbs HSC function leading to AML like disease
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary We found that posterior HOXA-associated HOTTIP lncRNA is aberrantly activated in MLL-rearranged AMLs and required for the posterior HOXA chromatin structure and gene expression. Knock-out of HOTTIP attenuates leukemic progressions of the transplanted humanized AML mice by blocking posterior HOXA-associated AML gene expression programs while the dCas-VP160 mediated reactivation of HOTTIP restores HOXA locus chromatin structure and HOXA9-A13 gene expression in the CBS7/9 boundary depleted AML cells. Finally, transgenic expression of HOTTIP lncRNA in mouse bone marrow hematopoietic cells resulted in perturbation of the balance of HSC self-renewal and differentiation and development of AML like disease by aberrant altering HOXA associated chromatin structure and transcription program. Thus, HOTTIP lncRNA acts as oncogene to reprogram leukemic associated chromatin and gene transcription.
Overall design We have finished the RNA-SEQ, ATAC-seq, ChIP-seq, CHIRP-seq, HiC-seq and whole exome-seq to investigate the role of lncRNA HOTTIP and CTCF boundaries in hematopoiesis and leukemogenesis. LSK cells (Lin- Sca1+ Kit+) were sorted by FACS from the bone marrow of WT and Hottip transgenic mice for RNA-seq, ATAC-seq assay. MOLM13 leukemia cells were used to perform the CHIRP-seq, RNA-seq, CHIP-seq and HiC-seq analysis.
Contributor(s) Luo H, Huang S
Citation(s) 31786140
Submission date May 29, 2018
Last update date Dec 03, 2019
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 (7)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (66)
GSM3161912 WT-RNA-seq-1
GSM3161913 WT-RNA-seq-2
GSM3161914 HOTTIP-KO-RNA-seq-1
BioProject PRJNA473439
SRA SRP149124

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SOFT formatted family file(s) SOFTHelp
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Supplementary file Size Download File type/resource
GSE114981_RAW.tar 19.5 Mb (http)(custom) TAR (of BED, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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