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| Status |
Public on Aug 14, 2020 |
| Title |
The C. elegans SET-2 histone methyltransferase maintains germline fate by preventing progressive transcriptomic deregulation across generations |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Chromatin factors contribute to germline maintenance by preserving a germline-appropriate transcriptional program. In the absence of the conserved histone H3 Lys4 (H3K4) methyltransferase SET-2, C. elegans germ cells progressively lose their identity over generations, leading to sterility. How this transgenerational loss of fertility results from the absence of SET-2 is unknown. Here we performed expression profiling across generations on germlines from mutant animals lacking SET-2 activity. We found that gene deregulation occurred in 2 steps: a priming step in early generations progressing to loss of fertility in later generations. By performing Within-Class Analysis (WCA), a derivative of Principal Component Analysis, we identified transcriptional signatures associated with SET-2 inactivation, both at the priming step and later on during loss of fertility. Further analysis showed that repression of germline genes, derepression of somatic programs, and X-chromosome desilencing through interference with PRC2-dependent repression, are priming events driving loss of germline identity in the absence of SET-2. Decreasing expression of identified priming genes, including the C/EBP homologue cebp-1 and TGF-b pathway components, was sufficient to delay the onset of sterility, suggesting that they individually contribute to the loss of germ cell fate. Altogether, our findings illustrate how the loss of a chromatin regulator at one generation can progressively deregulate multiple transcriptional and signaling programs, ultimately leading to loss of appropriate cell fate.
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| Overall design |
Transcriptome profiles of 3 independent lineages of set-2(bn129) gonads. Each lineage contains fertile F2 set-2 gonads, fertile F4 set-2 gonads, and sterile F4 set-2 gonads. Three replicates of set-2/qC1 gonads serves as a control.
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| Contributor(s) |
Robert VJ, Knutson AK, Rechtsteiner A, Yvert G, Strome S, Palladino F |
| Citation(s) |
33072747 |
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| Submission date |
Mar 23, 2019 |
| Last update date |
Oct 27, 2020 |
| Contact name |
Susan Strome |
| E-mail(s) |
sstrome@ucsc.edu
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| Organization name |
UC Santa Cruz
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| Department |
MCD Biology
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| Street address |
1156 High St
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| City |
Santa Cruz |
| State/province |
CA |
| ZIP/Postal code |
95064 |
| Country |
USA |
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| Platforms (2) |
| GPL18245 |
Illumina HiSeq 2500 (Caenorhabditis elegans) |
| GPL22765 |
Illumina HiSeq 4000 (Caenorhabditis elegans) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA528750 |
| SRA |
SRP189234 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE128746_RAW.tar |
1.5 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE128746_set2.DESeq2.outp_05.2018.csv.gz |
2.8 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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