Gcn5-Mediated Histone Acetylation Governs Nucleosome Dynamics in Spermiogenesis.
Dev Cell
; 51(6): 745-758.e6, 2019 12 16.
Article
em En
| MEDLINE
| ID: mdl-31761669
ABSTRACT
During mammalian spermatogenesis, germ cell chromatin undergoes dramatic histone acetylation-mediated reorganization, whereby 90%-99% of histones are evicted. Given the potential role of retained histones in fertility and embryonic development, the genomic location of retained nucleosomes is of great interest. However, the ultimate position and mechanisms underlying nucleosome eviction or retention are poorly understood, including several studies utilizing micrococcal-nuclease sequencing (MNase-seq) methodologies reporting remarkably dissimilar locations. We utilized assay for transposase accessible chromatin sequencing (ATAC-seq) in mouse sperm and found nucleosome enrichment at promoters but also retention at inter- and intragenic regions and repetitive elements. We further generated germ-cell-specific, conditional knockout mice for the key histone acetyltransferase Gcn5, which resulted in abnormal chromatin dynamics leading to increased sperm histone retention and severe reproductive phenotypes. Our findings demonstrate that Gcn5-mediated histone acetylation promotes chromatin accessibility and nucleosome eviction in spermiogenesis and that loss of histone acetylation leads to defects that disrupt male fertility and potentially early embryogenesis.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Espermatogênese
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Histonas
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Nucleossomos
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Fatores de Transcrição de p300-CBP
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article