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Missing the Mark: PRDM9-Dependent Methylation Is Required for Meiotic DSB Targeting

Rhea Kang1, Maciej J Zelazowski2, Francesca Cole1

  • 1Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USA; Program in Genetics and Epigenetics, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Science Park, Smithville, TX 78957, USA.

Molecular Cell
|March 3, 2018
PubMed

Insights

The PRDM9 protein

Area of Science:

  • Genetics
  • Epigenetics
  • Molecular Biology

Background:

  • PRDM9 protein is crucial for directing meiotic recombination hotspots.
  • Meiotic recombination hotspots are epigenetically marked by histone H3 methylation.
  • The precise role of PRDM9's methyltransferase activity and allele dominance in hotspot localization remains unclear.

Purpose of the Study:

  • To investigate whether PRDM9's methyltransferase activity is essential for hotspot localization.
  • To understand the mechanism behind the dominance of certain PRDM9 alleles in controlling hotspot distribution.

Main Methods:

  • The study involved analyzing the function of PRDM9 alleles and their methyltransferase activity.
  • Experimental approaches were used to assess hotspot localization in the presence of different PRDM9 variants.

Main Results:

  • PRDM9's methyltransferase activity was demonstrated to be necessary for the localization of meiotic recombination hotspots.
  • The methyltransferase activity of combined PRDM9 alleles was found to be additive.
  • Allele dominance in hotspot distribution correlates directly with the frequency of targeted sites.

Conclusions:

  • PRDM9's methyltransferase function is indispensable for establishing meiotic recombination hotspots.
  • The observed dominance of specific PRDM9 alleles is explained by the additive nature of their methyltransferase activity and the frequency of their target sites.

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