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| Status |
Public on Jun 22, 2020 |
| Title |
Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Autophagy is an essential cellular process that maintains homeostasis by recycling damaged organelles and nutrients during development and cellular stress. ZKSCAN3 is the sole identified master transcriptional repressor of autophagy in human cell lines. How ZKSCAN3 achieves autophagy repression at the mechanistic or organismal level however still remains to be elucidated. Furthermore, Zkscan3 knockout mice display no discernable autophagy-related phenotypes, suggesting that there may be substantial differences in the regulation of autophagy between normal tissues and tumor cell lines. Here, we demonstrate that vertebrate ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy repression. Expression of ZKSCAN3 in Drosophila prevents premature autophagy onset due to loss of M1BP function and conversely, M1BP expression in human cells can prevent starvation-induced autophagy due to loss of nuclear ZKSCAN3 function. In Drosophila ZKSCAN3 binds genome-wide to sequences targeted by M1BP and transcriptionally regulates the majority of M1BP-controlled genes, demonstrating the evolutionary conservation of the transcriptional repression of autophagy and allow the potential for transitioning the mechanisms, gene targets and plethora metabolic processes controlled by M1BP onto ZKSCAN3 and opens up Drosophila as a tool in studying the function of ZKSCAN3 in autophagy and tumourigenesis.
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| Overall design |
Fat bodies from 3rd instar (L3) feeding (L3F) or wandering (L3W) Drosophila melanogaster larvae and total RNA prepared. For L3W versus L3F analyses, fat bodies from wild-type female fat bodies were used. For M1BP RNAi analyses, fat bodies from male fat bodies with gonads removed were used (genotypes of cgGal4 crossed with either wild-type or MBP RNAi). For ZKSCAN3 analyses, fat bodies from male fat bodies with gonads removed were used (genotypes of cgGal4 crossed with either wild-type or HA::ZKSCAN3). For M1BP RNAi/ZKSCAN3 analyses, fat bodies from male fat bodies with gonads removed were used (genotypes of cgGal4 crossed with either wild-type or M1BP-RNAi;HA::ZKSCAN3). S2-DRSC Drosophila cells are stably transfected with HA-tagged vertebrate ZKSCAN3 or ZKSCAN4 (S2-DRSC:AbdA)and analysed for genomic binding of HA-ZKSCAN3 and ZKSCAN4
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| Contributor(s) |
Barthez M, Poplineau M, El-Refaey M, Caruso N, Graba Y, Saurin AJ |
| Citation(s) |
32541927 |
| |
| Submission date |
Apr 22, 2020 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Andrew J Saurin |
| E-mail(s) |
andrew.saurin@univ-amu.fr
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| Organization name |
IBDM / CNRS
|
| Street address |
Campus de Luminy
|
| City |
Marseille |
| ZIP/Postal code |
13009 |
| Country |
France |
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| Platforms (2) |
| GPL13304 |
Illumina HiSeq 2000 (Drosophila melanogaster) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA627409 |
| SRA |
SRP257903 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE149116_DGE_L3W_vs_L3F_dmel6_FDR01_logFC1.xlsx |
449.3 Kb |
(ftp)(http) |
XLSX |
| GSE149116_DGE_M1BPiZKSCAN3_vs_WT_dmel6_FDR01_logFC_ordered.txt.gz |
52.7 Kb |
(ftp)(http) |
TXT |
| GSE149116_DGE_M1BPi_vs_WT_dmel6_FDR01_logFC_ordered.txt.gz |
68.3 Kb |
(ftp)(http) |
TXT |
| GSE149116_DGE_ZKSCAN3_vs_WT_dmel6_FDR01_logFC_ordered.txt.gz |
2.2 Kb |
(ftp)(http) |
TXT |
| GSE149116_WT_M1BPi_ZKSCAN3_dmel6_exon_counts.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE149116_WT_female_F_W_dmel6_exon_counts.txt.gz |
920.7 Kb |
(ftp)(http) |
TXT |
| GSE149116_ZKSCAN3_S2_peaks.bed.gz |
143.6 Kb |
(ftp)(http) |
BED |
| GSE149116_ZKSCAN4_S2_peaks.bed.gz |
134.6 Kb |
(ftp)(http) |
BED |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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