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Series GSE160427 Query DataSets for GSE160427
Status Public on Dec 17, 2020
Title A Tumor Suppressor Enhancer of PTEN in T-cell development and leukemia
Organisms Homo sapiens; Mus musculus
Experiment type Other
Summary Long-range oncogenic enhancers play an important role in cancer. Yet, it remains unclear whether similar regulation of tumor suppressor genes is relevant. In this context, loss of expression of the tumor suppressor PTEN is associated with the pathogenesis of various cancers, including T-cell acute lymphoblastic leukemia (T-ALL). Here, we demonstrate that PTEN is regulated in T-cells by a distal enhancer (PE), which is targeted by recurrent focal deletions in T-ALL. This highly conserved regulatory element interacts with and transactivates the PTEN promoter. Consistently, PE deletion in T-ALL cells leads to reduced PTEN levels and proliferative advantage. Moreover, PE-null mice show reduced PTEN levels in the thymus and develop NOTCH1-induced T-ALL with faster kinetics. Furthermore, secondary loss of PE in established leukemias leads to accelerated progression and a gene expression signature driven by Pten loss. Altogether, our results identify PE as the first long-range tumor suppressor enhancer directly implicated in cancer.
Overall design This 4C-seq analysis of the PTEN locus uses human (DND41, HPBALL and JURKAT) and mouse (N1dE_PKM2 and HDdPEST) cells. In each case 4C-seq was done with a bait on the promoter and putative enhancer loci.
Contributor(s) Rocha PP
Citation(s) 33458694
Submission date Oct 29, 2020
Last update date Mar 18, 2021
Contact name Pedro P Rocha
Phone 3014022426
Organization name National Institutes of Health
Department NICHD
Lab Unit on Genome Structure and Regulation
Street address 6 Center Drive Building 6B 2B220
City Bethesda
State/province Maryland
ZIP/Postal code 20892-2785
Country USA
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (30)
GSM4873156 DND41_PTEN_promoter_rep1
GSM4873157 DND41_PTEN_promoter_rep2
GSM4873158 DND41_PTEN_promoter_rep3
BioProject PRJNA673187
SRA SRP289765

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Supplementary file Size Download File type/resource
GSE160427_RAW.tar 320.0 Kb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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