Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide map of H3K4me3 in HEK293 cells after PRDM9 expression


ABSTRACT: PRDM9 is a histone methyltransferase expressed in meiotic germ cells that determines the location of genetic recombination hotspots through binding of its allele-specific DNA binding domain. Here we characterize the genome-wide chromatin modification for two human PRDM9 alleles (A and C) in human cell lines. HEK293 cells were transfected with both alleles and an empty vector control. Resulting chromatin was subjected to H3K4me3 ChIP followed by high-throughput sequencing. We find that different PRDM9 allele largely modified chromatin in entirely different genomic regions in somatic cells determined by the protein's zinc-finger DNA binding domains. Many of the allele-specific peaks overlap sites of meiotic double-strand breaks found in vivo in human germ cells suggesting that transient expression of PRDM9 in somatic cells can reflect binding in vivo. Identify PRDM9-dependent H3K4me3 sites by comparing modified chromatin after expression of different human PRDM9 alleles in HEK293 cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Kenneth Paigen 

PROVIDER: E-GEOD-67673 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

Baker Christopher L CL   Petkova Pavlina P   Walker Michael M   Flachs Petr P   Mihola Ondrej O   Trachtulec Zdenek Z   Petkov Petko M PM   Paigen Kenneth K  

PLoS genetics 20150914 9


Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity,  ...[more]

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