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Series GSE214833 Query DataSets for GSE214833
Status Public on Apr 30, 2023
Title Hematopoiesis and cell growth are differentially regulated by TAL1 isoforms
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary T-cell acute lymphoblastic leukemia (T-ALL) protein 1 (TAL1) is a central transcription factor in hematopoiesis. The timing and level of TAL1 expression orchestrate the differentiation to specialized blood cells and its overexpression is the most common cause of T-ALL. Here we studied the two protein isoforms of TAL1, short and long, that are generated by the use of alternative promoters as well as by alternative splicing. We analyzed the expression of each isoform by deleting an enhancer or insulator, or by opening chromatin at the enhancer location. Our results show that each enhancer promotes expression from a specific TAL1 promoter. Expression from a specific promoter gives rise to a unique 5’ UTR with differential regulation of translation. In addition, the enhancers regulate TAL1 exon 3 alternative splicing by altering the chromatin at its location. Furthermore, our results indicate that TAL1-short binds more strongly to TAL1 E-protein partners and function as a stronger transcription factor than TAL1-long. Specifically TAL1-short has a unique transcription signature promoting apoptosis. Finally, expressing both isoforms in mice bone marrow, we found that while overexpression of both isoforms prevents lymphoid differentiation, expression of TAL-short alone reduced survival capability of hematopoietic stem cells. Furthermore, we found that TAL1-short promoted erythropoiesis and reduced cell survival in the AML cell line K562. While TAL1 and its partners are considered promising therapeutic targets in the treatment of T-ALL, our results show that TAL1-short could act as a tumor suppressor and suggest that altering TAL1 isoform’s ratio could be a preferred therapeutic approach.
 
Overall design We silenced endogenous TAL1 by stably transfecting Jurkat cells with inducible TAL1 shRNA targeting its 3’ UTR, and by that targeting only the endogenous mRNA. We continued by transfecting either empty vector, TAL1-short or TAL1-long and monitored total mRNA amount of the targets.
Web link https://pubmed.ncbi.nlm.nih.gov/37379322/
 
Contributor(s) Sharma A, Mistriel-Zerbib S, Najar RA, Salton M
Citation(s) 37379322
Submission date Oct 05, 2022
Last update date Jul 31, 2023
Contact name Inbar Plaschkes
Organization name HUJI
Department The Faculty of Medicine - Ein Kerem
Street address The Hebrew University of Jerusalem - Ein Kerem
City Jerusalem
ZIP/Postal code 91120
Country Israel
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (9)
GSM6616500 Jurkat shTAL1 Empty 1
GSM6616501 Jurkat shTAL1 Empty 2
GSM6616502 Jurkat shTAL1 Empty 3
Relations
BioProject PRJNA887369

Download family Format
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Supplementary file Size Download File type/resource
GSE214833_RNAseq_normCounts.txt.gz 1.0 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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