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Genetics. 2018 Jun;209(2):475-487. doi: 10.1534/genetics.118.300565. Epub 2018 Apr 19.

Interrogating the Functions of PRDM9 Domains in Meiosis.

Author information

1
Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences (USUHS), Bethesda, Maryland 20814.
2
Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland 20892.
3
Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland 20892 Galina.Petukhova@usuhs.edu rc10d@nih.gov rdcamerini@nih.gov.
4
Department of Biochemistry and Molecular Biology, Uniformed Services University of Health Sciences (USUHS), Bethesda, Maryland 20814 Galina.Petukhova@usuhs.edu rc10d@nih.gov rdcamerini@nih.gov.

Abstract

Homologous recombination is required for proper segregation of homologous chromosomes during meiosis. It occurs predominantly at recombination hotspots that are defined by the DNA binding specificity of the PRDM9 protein. PRDM9 contains three conserved domains typically involved in regulation of transcription; yet, the role of PRDM9 in gene expression control is not clear. Here, we analyze the germline transcriptome of Prdm9-/- male mice in comparison to Prdm9+/+ males and find no apparent differences in the mRNA and miRNA profiles. We further explore the role of PRDM9 in meiosis by analyzing the effect of the KRAB, SSXRD, and post-SET zinc finger deletions in a cell culture expression system and the KRAB domain deletion in mice. We found that although the post-SET zinc finger and the KRAB domains are not essential for the methyltransferase activity of PRDM9 in cell culture, the KRAB domain mutant mice show only residual PRDM9 methyltransferase activity and undergo meiotic arrest. In aggregate, our data indicate that domains typically involved in regulation of gene expression do not serve that role in PRDM9, but are likely involved in setting the proper chromatin environment for initiation and completion of homologous recombination.

KEYWORDS:

KRAB domain; PRDM9; homologous recombination; meiosis

PMID:
29674518
PMCID:
PMC5972421
DOI:
10.1534/genetics.118.300565
[Indexed for MEDLINE]
Free PMC Article

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