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Journal Articles EMBO Reports Year : 2023

DOT1L regulates chromatin reorganization and gene expression during sperm differentiation

Mélina Blanco
  • Function : Author
Laila El Khattabi
Clara Gobé
  • Function : Author
Marion Crespo
  • Function : Author
Manon Coulée
  • Function : Author
Alberto de la Iglesia
Côme Ialy-Radio
  • Function : Author
Clementine Lapoujade
  • Function : Author
Maëlle Givelet
  • Function : Author
Marion Delessard
Ivan Seller-Corona
Kosuke Yamaguchi
  • Function : Author
Fred van Leeuwen
Alban Lermine
  • Function : Author
Yuki Okada
  • Function : Author
Romain Daveau
  • Function : Author
Rafael Oliva
Pierre Fouchet
  • Function : Author
Ahmed Ziyyat
Delphine Pflieger
  • Function : Author
Julie Cocquet

Abstract

Abstract Spermatozoa have a unique genome organization. Their chromatin is almost completely devoid of histones and is formed instead of protamines, which confer a high level of compaction and preserve paternal genome integrity until fertilization. Histone‐to‐protamine transition takes place in spermatids and is indispensable for the production of functional sperm. Here, we show that the H3K79‐methyltransferase DOT1L controls spermatid chromatin remodeling and subsequent reorganization and compaction of the spermatozoon genome. Using a mouse model in which Dot1l is knocked‐out (KO) in postnatal male germ cells, we found that Dot1l ‐KO sperm chromatin is less compact and has an abnormal content, characterized by the presence of transition proteins, immature protamine 2 forms and a higher level of histones. Proteomic and transcriptomic analyses performed on spermatids reveal that Dot1l ‐KO modifies the chromatin prior to histone removal and leads to the deregulation of genes involved in flagellum formation and apoptosis during spermatid differentiation. As a consequence of these chromatin and gene expression defects, Dot1l ‐KO spermatozoa have less compact heads and are less motile, which results in impaired fertility.
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Dates and versions

hal-04253697 , version 1 (23-10-2023)

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Mélina Blanco, Laila El Khattabi, Clara Gobé, Marion Crespo, Manon Coulée, et al.. DOT1L regulates chromatin reorganization and gene expression during sperm differentiation. EMBO Reports, 2023, 24 (6), ⟨10.15252/embr.202256316⟩. ⟨hal-04253697⟩
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