Sperm histone H3 lysine 4 trimethylation is altered in a genetic mouse model of transgenerational epigenetic inheritance.
Animals
Cellular Reprogramming
Chromatin
/ metabolism
Chromatin Immunoprecipitation Sequencing
Embryo, Mammalian
/ metabolism
Epigenesis, Genetic
Gene Ontology
Genetic Loci
Histone Demethylases
/ genetics
Histones
/ metabolism
Lysine
/ metabolism
Male
Methylation
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
Promoter Regions, Genetic
Spermatocytes
/ metabolism
Spermatogenesis
/ genetics
Spermatozoa
/ metabolism
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 11 2020
18 11 2020
Historique:
accepted:
15
10
2020
revised:
11
08
2020
received:
21
02
2020
pubmed:
18
10
2020
medline:
29
12
2020
entrez:
17
10
2020
Statut:
ppublish
Résumé
Advancing the molecular knowledge surrounding fertility and inheritance has become critical given the halving of sperm counts in the last 40 years, and the rise in complex disease which cannot be explained by genetics alone. The connection between both these trends may lie in alterations to the sperm epigenome and occur through environmental exposures. Changes to the sperm epigenome are also associated with health risks across generations such as metabolic disorders and cancer. Thus, it is imperative to identify the epigenetic modifications that escape reprogramming during spermatogenesis and embryogenesis. Here, we aimed to identify the chromatin signature(s) involved in transgenerational phenotypes in our genetic mouse model of epigenetic inheritance that overexpresses the histone demethylase KDM1A in their germ cells. We used sperm-specific chromatin immunoprecipitation followed by in depth sequencing (ChIP-seq), and computational analysis to identify whether differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3), and histone H3 lysine 27 trimethylation (H3K27me3) serve as mechanisms for transgenerational epigenetic inheritance through the paternal germline. Our analysis on the sperm of KDM1A transgenic males revealed specific changes in H3K4me3 enrichment that predominantly occurred independently from bivalent H3K4me3/H3K27me3 regions. Many regions with altered H3K4me3 enrichment in sperm were identified on the paternal allele of the pre-implantation embryo. These findings suggest that sperm H3K4me3 functions in the transmission of non-genetic phenotypes transgenerationally.
Identifiants
pubmed: 33068438
pii: 5929231
doi: 10.1093/nar/gkaa712
pmc: PMC7672453
doi:
Substances chimiques
Chromatin
0
Histones
0
histone H3 trimethyl Lys4
0
Histone Demethylases
EC 1.14.11.-
KDM1A protein, human
EC 1.5.-
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11380-11393Subventions
Organisme : CIHR
ID : 350129
Pays : Canada
Informations de copyright
© ? The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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