|
| Status |
Public on Aug 01, 2012 |
| Title |
AGO4 Regulates Entry into Meiosis and Influences Silencing of Sex Chromosomes in the Male Mouse Germline |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
The four mammalian Argonaute family members are thought to share redundant functions in the microRNA pathway, yet only AGO2 possesses the catalytic "slicer" function required for RNA
interference. Whether AGO1, AGO3, or AGO4 possess specialized functions remains unclear. Here, we Series_summary = show that AGO4 localizes to spermatocyte nuclei during meiotic prophase I, specifically at sites of asynapsis and in the transcriptionally silenced XY sub-domain, the sex body. We generated Ago4 knockout mice and show that Ago4-/- spermatogonia initiate meiosis early, resulting from premature
induction of retinoic acid-response genes. During prophase I, the sex body assembles incorrectly in Ago4-/- mice, leading to disrupted meiotic sex chromosome inactivation (MSCI). This is associated
with a dramatic loss of microRNAs, >20% of which arise from the X chromosome. Loss of AGO4 results in increased AGO3 in spermatocytes, indicating some degree of redundancy. Thus, AGO4 regulates
meiotic entry and MSCI in mammalian germ cells, implicating small RNA pathways in these processes.
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| |
|
| Overall design |
mRNA transcripts were isolated and prepared using pachytene spermatocytes, pre-meiotic testes and other tissues from Ago4+/+ and Ago4-/- littermates and sequenced using Illumina HiSeq2000.
small RNA transcripts were isolated and prepared using pachytene spermatocytes from adult Ago4+/+ and Ago4-/- littermates and sequenced using Illumina GAII.
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| |
|
| Contributor(s) |
Modzelewski MA, Stephanie H, Andrew G, Paula CE |
| Citation(s) |
22863743 |
| Submission date |
Jul 25, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Stephanie Renee Hilz |
| E-mail(s) |
stephanie.hilz@gmail.com
|
| Organization name |
Cornell University
|
| Street address |
Biotech 445, Cornell University
|
| City |
Ithaca |
| ZIP/Postal code |
14850 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
|
| Samples (10)
|
|
| Relations |
| BioProject |
PRJNA171334 |
| SRA |
SRP014578 |
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