Transcriptomics

Dataset Information

356

AGO4 Regulates Entry into Meiosis and Influences Silencing of Sex Chromosomes in the Male Mouse Germline


ABSTRACT: 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. 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.

ORGANISM(S): Mus musculus  

SUBMITTER: Modzelewski A Modzelewski   Grimson Andrew  Hilz Stephanie  Stephanie Renee Hilz  Cohen E Paula 

PROVIDER: E-GEOD-39652 | ArrayExpress | 2012-08-01

SECONDARY ACCESSION(S): SRP014578GSE39652PRJNA171334

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

AGO4 regulates entry into meiosis and influences silencing of sex chromosomes in the male mouse germline.

Modzelewski Andrew J AJ   Holmes Rebecca J RJ   Hilz Stephanie S   Grimson Andrew A   Cohen Paula E PE  

Developmental cell 20120802 2


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 RNAi. Whether AGO1, AGO3, or AGO4 possesses specialized functions remains unclear. Here we show that AGO4 localizes to spermatocyte nuclei during meiotic prophase I, specifically at sites of asynapsis and the transcriptionally silenced XY subdomain, the sex body. We generated Ago4 knockout mice and show that Ago4(-/-) s  ...[more]

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