DOT1L regulates chromatin reorganization and gene expression during sperm differentiation.
H3K79 methylation
flagellum development
gene regulation
histone-to-protamine transition
spermatogenesis
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 06 2023
05 06 2023
Historique:
revised:
31
03
2023
received:
17
10
2022
accepted:
13
04
2023
medline:
6
6
2023
pubmed:
26
4
2023
entrez:
26
4
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37099396
doi: 10.15252/embr.202256316
pmc: PMC10240200
doi:
Substances chimiques
Chromatin
0
Histones
0
Dot1l protein, mouse
EC 2.1.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e56316Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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