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Series GSE260783 Query DataSets for GSE260783
Status Public on May 22, 2024
Title Effect of VGLL2-NCOA2, TEAD1-NCOA2 and YAP5SA overexpression on mRNA expression in HEK293T cells (RNA-Seq)
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The vestigial like family proteins (VGLL) are thought to regulate transcription by interacting with the TEA domain transcription factors (TEAD), the primary mediators of the Hippo pathway. However, the functional regulation of VGLL proteins remains poorly characterized. Here, we explored the molecular mechanism of two VGLL2 and TEAD1 fusion proteins generated by recurrent translocations in spindle cell rhabdomyosarcoma. We demonstrated that, compared to VGLL2 and TEAD1 alone, VGLL2-NCOA2 and TEAD1-NCOA2 act as strong transcriptional activators of TEAD-mediated transcription. Although VGLL2-NCOA2 and Yes1 associated transcriptional regulator (YAP) control overlapping transcriptional programs and chromatin landscapes, the downstream transcription induced by the fusion proteins does not require YAP and WW domain containing transcription regulator 1 (TAZ). Furthermore, VGLL2-NCOA2 and TEAD1-NCOA2 fusions engage distinct epigenetic regulation by recruiting E1A binding protein p300 (p300) to drive TEAD-dependent transcription. We showed that small molecule p300 inhibition can suppress VGLL2-NCOA2 and TEAD1-NCOA2-induced oncogenic transformation both in vitro and in vivo. Overall, our data reveal a tumorigenic mechanism of VGLL and TEAD fusion proteins that is related to the Hippo pathway but independent of YAP/TAZ, suggesting potential therapeutic strategies for tumors carrying VGLL, TEAD, or nuclear receptor coactivator (NCOA) gene rearrangements.
 
Overall design To investigate the effect of VGLL2-NCOA2 fusion protein, TEAD1-NCOA2 fusion protein and YAP5SA protein on gene transcription, plasmids were transfected into HEK293T cells and mRNA were detected by RNA-seq. HEK293T cells transfected pcDNA3.1 plasmids were used as control group. HEK293T cells with transient transfection of VGLL2-NCOA2, TEAD1-NCOA2 or YAP5SA were used as experimental group. The mRNA expression level was detected by RNA-seq.
 
Contributor(s) Mao J, Guo S, Hu X, Ma L
Citation(s) 38746415
Submission date Mar 04, 2024
Last update date May 22, 2024
Contact name Susu Guo
E-mail(s) susuguo2022@gmail.com
Phone +17745190409
Organization name UMASS Chan Medical School
Street address 7 Pocono Road
City WORCESTER
State/province MA
ZIP/Postal code 01605
Country USA
 
Platforms (1)
GPL20795 HiSeq X Ten (Homo sapiens)
Samples (12)
GSM8124532 Control1
GSM8124533 VN1
GSM8124534 TN1
This SubSeries is part of SuperSeries:
GSE260784 Vestigial like family protein
Relations
BioProject PRJNA1083487

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
GSE260783_RNA_seq_fpkm.xlsx 23.2 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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