Interrogating the Functions of PRDM9 Domains in Meiosis

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 tra...

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Bibliographic Details
Published in:	Genetics (Austin) Vol. 209; no. 2; pp. 475 - 487
Main Authors:	Thibault-Sennett, Sarah, Yu, Qi, Smagulova, Fatima, Cloutier, Jeff, Brick, Kevin, Camerini-Otero, R Daniel, Petukhova, Galina V
Format:	Journal Article
Language:	English
Published:	United States Genetics Society of America 01-06-2018 Oxford University Press
Subjects:	Amino acids Animals Binding sites Cell culture Cell Line Chromatin Chromosomes Clonal deletion Deoxyribonucleic acid DNA DNA methylation Female Gametogenesis Gene expression Gene regulation Genetics Genomes Histone-Lysine N-Methyltransferase - chemistry Histone-Lysine N-Methyltransferase - genetics Histone-Lysine N-Methyltransferase - metabolism Homologous recombination Homology Investigations Life Sciences Male Males Meiosis Methyltransferase Mice Mice, Inbred BALB C Mice, Inbred C57BL MicroRNAs miRNA Protein Domains Proteins Recombination hot spots Ribonucleic acid RNA Transcription Transcriptome Zinc Zinc finger proteins Zinc Fingers KRAB domain PRDM9 meiosis homologous recombination
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Summary:	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 male mice in comparison to 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC5972421 These authors contributed equally to this work. Present address: 9 Avenue du Professeur Léon Bernard, 35000 Rennes, France.
ISSN:	1943-2631 0016-6731 1943-2631
DOI:	10.1534/genetics.118.300565