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Series GSE227972 Query DataSets for GSE227972
Status Public on Mar 06, 2024
Title MY-COMP, an inhibitor of the transcriptional activity of YAP-B-MYB, identifies NEK2 as a novel mediator of YAP oncogenesis in uveal melanoma cells [CUT&RUN]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Activation of YAP is frequently observed in cancer and is associated with poor outcomes, making it an attractive target for therapeutic intervention. Previous studies have mainly focused on blocking the interaction of YAP with TEAD transcription factors. Here we took a different approach by interfering with the binding of YAP to the transcription factor B-MYB using MY-COMP, a fragment of B-MYB containing the YAP binding domain fused to a nuclear localization signal. We found that expression of MY-COMP inhibited the binding of B-MYB to YAP, resulting in growth defects, nuclear abnormalities and polyploidization in HeLa cells.
Additionally, MY-COMP interfered with normal cell cycle progression of YAP-dependent uveal melanoma cells, but its effects were much weaker in YAP-independent cutaneous melanoma cell lines. MY-COMP antagonized the YAP-dependent expression of MMB-regulated cell cycle genes, providing an explanation for the observed phenotypes. We identified NIMA-related kinase (NEK2) as a candidate target downstream of YAP and B-MYB, contributing to the transformation of YAP-dependent uveal tumor cell lines. Overall, our findings suggest that targeting selected YAP-MMB regulated genes such as NEK2 or inhibiting the WW-domains of YAP to suppress YAP-regulated cell cycle genes could provide a novel mechanism to antagonize the pro-tumorigenic functions of YAP.
 
Overall design CUT&RUN sequencing was done with uveal melanoma cells (92.1) without further treatment in order to identify chromatin bound proteins YAP, H3K4me1, H3K4me3, H3K27ac and H4ac. For CUT&Run sequencing samples, the immunoprecipitation of digested DNA was done for YAP, H3K4me1, H3K4me3, H3K27ac and H4ac, using th below listed antibodies. As control, DNA was sequenced following immunoprecipitation with an unspecific IgG antibody.
 
Contributor(s) Gertzmann D, Liss F, Gruendl M, Baehner L, Schoeffler V, Ade CP, von Eyss B, Gaubatz S
Citation(s) 38182898
Submission date Mar 22, 2023
Last update date Mar 07, 2024
Contact name Carsten P Ade
Organization name University of Wuerzburg
Department Lehrstuhl Biochemie und Molekularbiologie
Lab AG Martin Eilers
Street address Am Hubland
City Wuerzburg
ZIP/Postal code 97074
Country Germany
 
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (8)
GSM7111604 CnR3_IgG
GSM7111605 CnR3_H3K4me3
GSM7111606 CnR3_H3K27ac
This SubSeries is part of SuperSeries:
GSE227974 MY-COMP, an inhibitor of the transcriptional activity of YAP-B-MYB, identifies NEK2 as a novel mediator of YAP oncogenesis in uveal melanoma cells
Relations
BioProject PRJNA947600

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE227972_RAW.tar 3.5 Gb (http)(custom) TAR (of BIGWIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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