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Series GSE90460 Query DataSets for GSE90460
Status Public on Nov 24, 2016
Title A Curcumin-Based CBP HAT Inhibitor Modulates the Transcription Functions of Tumor Suppressor p53
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Coactivator CREB-binding protein (CBP) regulates the transcription program of p53, which orchestrates cellular responses to a wide-range of stress conditions that cause genomic instability. Given the ability of CBP to regulate transcription by multiple mechanisms, the biological significance of its acetylation-directed functions may not be fully clear. The present study demonstrates the development of a curcumin-derived modulator of CBP histone acetyl-transferase (HAT) activity, CM354, which inhibits acetylation of p53 on lysine 382, acetylation of histone H3K27 and autoacetylation of CBP. These epigenetic changes are concomitant with downregulation of p53 and CBP functions, which facilitate the presence of histone methyl transferase, Enhancer of zeste homolog 2 (EZH2), on CDKNI1A/p21 promoter, thereby, enhancing the level of trimethylation on H3K27. Treatment with CM354 results in the activation of PARP and the abrogation of cellular growth. Genome-wide network analysis depicts that CM354 could alter cell-fate by enrichment of chromatin H3K27 methylation and activation of the polycomb group of proteins. Though previously reported HAT inhibitors act at higher concentrations and lack cell permeability, the present study shows the impact of modulating endogenous CBP HAT activity on chromatin landscape and p53 functions.
Overall design Gene expression in human U2OS cell lines after treatment of CM354 (1.5uM), Doxorubicin (300ng/ml), the combination of the two drugs, as well as the untreated control was measured. Each condition is performed in duplicates.
Contributor(s) Ma'ayan A, Mujtaba S
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Submission date Nov 23, 2016
Last update date Nov 27, 2018
Contact name Zichen Wang
Organization name Icahn School of Medicine at Mount Sinai
Department Pharmacological Sciences
Lab Avi Ma'ayan
Street address 1468 Madison Ave
City New York
State/province NY
ZIP/Postal code 10029
Country USA
Platforms (1)
GPL13607 Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version)
Samples (8)
GSM2401529 S1_U2OS_untreated
GSM2401530 S2_U2OS_CM354
GSM2401531 S3_U2OS_Dox
BioProject PRJNA354786

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Supplementary file Size Download File type/resource
GSE90460_RAW.tar 103.5 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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