|
Status |
Public on May 22, 2012 |
Title |
Genetic recombination is directed away from functional genetic sites in mice. |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
Genetic recombination occurs during meiosis, the key developmental program of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyl-transferase, PRDM9, the product of the only known speciation gene in mammals. PRDM9 is thought to determine the preferred recombination sites - recombination hotspots - through sequence-specific binding of its highly polymorphic multi-Zn-finger domain. Nevertheless, Prdm9 knockout mice are proficient at initiating recombination. Here we map and analyze the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F1 hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the remarkable exception of the pseudoautosomal region – the only area of the genome that undergoes recombination in 100% of cells. Surprisingly, hotspots are still observed in Prdm9 knockout mice and as in wild-type, these hotspots are found at H3K4 trimethylation marks. However, in the absence of PRDM9, the majority of recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene promoter regions and other functional genomic elements.
|
|
|
Overall design |
Detection of meiotic double strand breaks in mouse testis and comparison with H3K4me3 marks.
|
|
|
Contributor(s) |
Brick K, Smagulova F, Khil P, Camerini-Otero R, Petukhova G |
Citation(s) |
22660327 |
Submission date |
Feb 02, 2012 |
Last update date |
Jun 25, 2020 |
Contact name |
Kevin Brick |
E-mail(s) |
brickkm@mail.nih.gov, kevbrick@gmail.com, brickkm@niddk.nih.gov
|
Organization name |
NIDDK
|
Department |
GBB
|
Street address |
5/205 Memorial Drive
|
City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
|
|
Platforms (2) |
GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
Samples (17)
|
|
Relations |
SRA |
SRP010715 |
BioProject |
PRJNA152299 |
Supplementary file |
Size |
Download |
File type/resource |
GSE35498_13R_DSB_hotspots.bedGraph.gz |
161.4 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_13R_H3K4me3_peaks.bedGraph.gz |
1007.9 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_9R_DSB_hotspots.bedGraph.gz |
155.6 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_9R_H3K4me3_peaks.bedGraph.gz |
1.0 Mb |
(ftp)(http) |
BEDGRAPH |
GSE35498_B6_DSB_hotspots.bedGraph.gz |
191.5 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_B6_H3K4me3_peaks.bedGraph.gz |
877.9 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_F1_DSB_hotspots.bedGraph.gz |
166.0 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_PRDM9_DSB_hotspots.bedGraph.gz |
260.2 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_PRDM9_H3K4me3_Liver_peaks.bedGraph.gz |
441.0 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_PRDM9_H3K4me3_Testis_peaks.bedGraph.gz |
949.6 Kb |
(ftp)(http) |
BEDGRAPH |
GSE35498_RAW.tar |
3.8 Gb |
(http)(custom) |
TAR (of BED) |
GSE35498_SPO11_H3K4me3_peaks.bedGraph.gz |
809.1 Kb |
(ftp)(http) |
BEDGRAPH |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |