PRDM9 activity depends on HELLS and promotes local 5-hydroxymethylcytosine enrichment.
5-Methylcytosine
/ analogs & derivatives
Animals
Binding Sites
DNA Breaks, Double-Stranded
DNA Helicases
/ metabolism
Endodeoxyribonucleases
/ metabolism
HeLa Cells
Histone-Lysine N-Methyltransferase
/ genetics
Homologous Recombination
Humans
Male
Mice
Mice, Knockout
Proteomics
Spermatocytes
/ cytology
Testis
/ metabolism
5hmC
HELLS
PRDM9
chromosomes
gene expression
genetics
genomics
lsh
meiosis
mouse
recombination
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
13 10 2020
13 10 2020
Historique:
received:
20
03
2020
accepted:
16
09
2020
pubmed:
14
10
2020
medline:
15
5
2021
entrez:
13
10
2020
Statut:
epublish
Résumé
Meiotic recombination starts with the formation of DNA double-strand breaks (DSBs) at specific genomic locations that correspond to PRDM9-binding sites. The molecular steps occurring from PRDM9 binding to DSB formation are unknown. Using proteomic approaches to find PRDM9 partners, we identified HELLS, a member of the SNF2-like family of chromatin remodelers. Upon functional analyses during mouse male meiosis, we demonstrated that HELLS is required for PRDM9 binding and DSB activity at PRDM9 sites. However, HELLS is not required for DSB activity at PRDM9-independent sites. HELLS is also essential for 5-hydroxymethylcytosine (5hmC) enrichment at PRDM9 sites. Analyses of 5hmC in mice deficient for SPO11, which catalyzes DSB formation, and in PRDM9 methyltransferase deficient mice reveal that 5hmC is triggered at DSB-prone sites upon PRDM9 binding and histone modification, but independent of DSB activity. These findings highlight the complex regulation of the chromatin and epigenetic environments at PRDM9-specified hotspots.
Identifiants
pubmed: 33047671
doi: 10.7554/eLife.57117
pii: 57117
pmc: PMC7599071
doi:
pii:
Substances chimiques
5-hydroxymethylcytosine
1123-95-1
5-Methylcytosine
6R795CQT4H
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
PRDM9 protein, human
EC 2.1.1.43
prdm9 protein, mouse
EC 2.1.1.43
Endodeoxyribonucleases
EC 3.1.-
meiotic recombination protein SPO11
EC 3.1.-
DNA Helicases
EC 3.6.4.-
HELLS protein, human
EC 5.99.-
Hells protein, mouse
EC 5.99.-
Banques de données
GEO
['GSE145768']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : ERC
ID : 322788
Pays : International
Organisme : MSDAVenir
ID : Gene-IGH
Pays : International
Organisme : European Research Council
ID : 322788
Pays : International
Informations de copyright
© 2020, Imai et al.
Déclaration de conflit d'intérêts
YI, MB, JC, MT, SU, TR, FB, CG No competing interests declared, Bd Reviewing editor, eLife
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