PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration.
Genome Res
; 24(5): 724-32, 2014 May.
Article
in En
| MEDLINE
| ID: mdl-24604780
ABSTRACT
In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots. Their locations are predominantly determined by the zinc finger protein PRDM9, which binds to DNA in hotspots and subsequently uses its SET domain to locally trimethylate histone H3 at lysine 4 (H3K4me3). This sets the stage for double-strand break (DSB) formation and reciprocal exchange of DNA between chromatids, forming Holliday junctions. Here we report genome-wide analyses of PRDM9-dependent histone modifications using two inbred mouse strains differing only in their PRDM9 zinc finger domain. We show that PRDM9 binding actively reorganizes nucleosomes into a symmetrical pattern, creating an extended nucleosome-depleted region. These regions are centered by a consensus PRDM9 binding motif, whose location and identity was confirmed in vitro. We also show that DSBs are centered over the PRDM9 binding motif within the nucleosome-depleted region. Combining these results with data from genetic crosses, we find that crossing-over is restricted to the region marked by H3K4me3. We suggest that PRDM9-modified nucleosomes create a permissible environment that first directs the location of DSBs and then defines the boundaries of Holliday junction branch migration.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nucleosomes
/
Protein Processing, Post-Translational
/
Histone-Lysine N-Methyltransferase
/
DNA, Cruciform
Limits:
Animals
Language:
En
Journal:
Genome Res
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA
Year:
2014
Document type:
Article