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Series GSE161919 Query DataSets for GSE161919
Status Public on Jun 15, 2021
Title The H3.3K27M oncohistone antagonizes reprogramming in Drosophila
Organism Drosophila melanogaster
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Development proceeds by the activation of genes by transcription factors and the inactivation of others by chromatin-mediated gene silencing. In some cases development can be reversed or redirected by mis-expression of master regulator transcription factors. This must involve the activation of previously silenced genes, and such developmental aberrations are thought to underlie a variety of cancers. Here, we express the wing-specific Vestigial master regulator to reprogram the developing eye, and test the role of silencing in reprogramming using an H3.3K27M oncohistone mutation that dominantly inhibits histone H3K27 trimethylation. We find that expression of the oncohistone blocks eye-to-wing reprogramming. CUT&Tag chromatin profiling of mutant tissues shows that H3K27me3 domains are globally reduced with oncohistone expression, suggesting that previous developmental programs must be silenced for effective transformation. Strikingly, mis-expressed Vg and H3.3K27M synergize to stimulate overgrowth of eye tissue, a phenotype that resembles that of mutations in Polycomb Repressive Complex 1 components. Our results imply that growth dysregulation can result from the simple combination of crippled silencing and transcription factor mis-expression, an effect that may explain the origins of oncohistone-bearing cancers.
 
Overall design We used Cleavage under targets and Tagmentation (Cut-and-Tag), a chromatin profiling strategy in which antibody-targeted controlled integration of DNA sequencing adapters produces libraries for paired-end DNA sequencing.
 
Contributor(s) Ahmad K, Henikoff S
Citation(s) 34280185
Submission date Nov 20, 2020
Last update date Jul 22, 2021
Contact name Jorja Henikoff
E-mail(s) jorja@fhcrc.org
Phone 206-667-4850
Organization name Fred Hutchinson Cancer Research Center
Department Basic Sciences
Lab Henikoff
Street address 1100 Fairview AV N, A1-162
City Seattle
State/province WA
ZIP/Postal code 98109-1024
Country USA
 
Platforms (1)
GPL17275 Illumina HiSeq 2500 (Drosophila melanogaster)
Samples (107)
GSM4923351 eyGAL_H3.3K27M_eye_H3K27M_1_(20201026_KA_DmEc_1802_D3B5T)
GSM4923352 eyGAL_H3.3K27M_eye_H3K27M_2_(20201026_KA_DmEc_1803_D3B5T)
GSM4923353 eyGAL_H3.3K27M_eye_H3K27me3_1_(20201026_KA_DmEc_1800_187)
Relations
BioProject PRJNA679825
SRA SRP293534

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
GSE161919_RAW.tar 847.5 Mb (http)(custom) TAR (of BED, BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
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