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The PRDM9 KRAB domain is required for meiosis and involved in protein interactions

Yukiko Imai1, Frédéric Baudat1, Miguel Taillepierre2

  • 1Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, 141 rue de la cardonille, 34396, Montpellier cedex 05, France.

Chromosoma
|May 21, 2017
PubMed

Insights

The Krüppel-associated box (KRAB) domain of PR domain-containing protein 9 (PRDM9) is crucial for its function in regulating meiotic recombination hotspots. Its interaction with CXXC1 suggests conserved mechanisms for double-strand break formation in mouse meiosis.

Area of Science:

  • Genetics
  • Molecular Biology
  • Reproductive Biology

Background:

  • PR domain-containing protein 9 (PRDM9) is a key regulator of meiotic recombination hotspots in mammals.
  • PRDM9 utilizes its DNA-binding domain and histone modifications for hotspot localization.
  • PRDM9 possesses a unique Krüppel-associated box (KRAB) domain with predicted protein interaction functions.

Purpose of the Study:

  • To investigate the functional significance of the KRAB domain in mouse PRDM9.
  • To identify proteins interacting with the PRDM9 KRAB domain.
  • To elucidate the role of these interactions in meiotic double-strand break (DSB) formation.

Main Methods:

  • Truncation of the KRAB domain in mouse PRDM9.
  • Yeast two-hybrid assays to identify interacting proteins.
  • Analysis of meiotic prophase and gametogenesis in mutant mice.
  • Investigating protein-protein interactions involving CXXC1 and IHO1.

Main Results:

  • Truncation of the PRDM9 KRAB domain resulted in loss of function, affecting meiotic prophase and gametogenesis.
  • CXXC1, a COMPASS complex member, was identified as a PRDM9 KRAB-interacting protein.
  • CXXC1 also interacts with IHO1, a component of the meiotic DSB machinery.

Conclusions:

  • The KRAB domain of PRDM9 is essential for its meiotic functions.
  • PRDM9 interacts with the meiotic DSB machinery via CXXC1.
  • These molecular interactions suggest conserved mechanisms for regulating meiotic DSB formation in mouse meiosis.
Keywords:
CXXC1IHO1MeiosisPRDM9 KRAB domainProtein interactionsRecombination

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