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Series GSE57431 Query DataSets for GSE57431
Status Public on Apr 08, 2016
Title HEXIM1 is induced by DHODH inhibition to suppress melanoma [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Recent evidence suggests that leflunomide, a DHODH inhibitor, disrupts neural crest development and melanoma pathogenesis via inhibiting transcription elongation. Here, we provide evidence that a transcriptional regulator, HEXIM1, is upregulated in response to leflunomide. HEXIM1 is assembled into the 7SK snRNP complex to sequester and inhibit the kinase P-TEFb. P-TEFb triggers elongation by phosphorylating RNA polymerase II and pausing factors. Knockdown of hexim in zebrafish rescues the effects of leflunomide. HEXIM1 expression is low in human melanoma. In addition, HEXIM1 overexpression can suppress melanoma onset in zebrafish. Increased HEXIM1 expression, in response to low nucleotides triggered by DHODH inhibition, sequesters P-TEFb away from melanoma pathogenesis, proliferation and cell cycle genes based on GRO-seq and ChIP-seq analyses. This reduces productive elongation at genes that maintain the tumorigenic state. Our study illustrates that HEXIM1 is a tumor suppressor that responds to cell stress, consequently inhibiting productive elongation of proliferative genes in melanoma.
Overall design ChIP-seq analysis of HEXIM1 and CDK9 chromatin binding in human A375 melanoma cells treated with either DMSO or 25uM A771726 for 48 hrs.
Contributor(s) Tan JL, Yang S, Fan ZP, Zhou Y, Young RA, Zon LI
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Submission date May 08, 2014
Last update date May 15, 2019
Contact name Leonard Zon
Organization name Boston Children's Hospital
Department Oncology/Hematology
Street address 1 Blackfan Circle
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (6)
GSM1382439 Input ChIP on DMSO-treated cells
GSM1382440 Input ChIP on A771726-treated cells
GSM1382441 CDK9 ChIP on DMSO-treated cells
This SubSeries is part of SuperSeries:
GSE57432 HEXIM1 is induced by DHODH inhibition to suppress melanoma
BioProject PRJNA246458
SRA SRP041794

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Supplementary file Size Download File type/resource
GSE57431_RAW.tar 569.3 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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