PR domainpositive-regulatory domain zinc finger protein 9 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''PRDM9''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. PRDM9 is responsible for positioning

recombination hotspot Recombination hotspots are regions in a genome that exhibit elevated rates of recombination relative to a neutral expectation. The recombination rate within hotspots can be hundreds of times that of the surrounding region. Recombination hotspots re ...

s during

meiosis Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately ...

by binding a DNA sequence motif encoded in its zinc finger domain. PRDM9 is the only speciation gene found so far in mammals, and is one of the fastest evolving genes in the genome.

Domain Architecture

PRDM9 has multiple domains including

KRAB KRAB (106.1 FM, "Alt 106.1") is a commercial alternative rock music radio station in Greenacres, California, broadcasting to the Bakersfield, California, area. The station is owned by iHeartMedia, Inc. Its studios are located in southwest Ba ...

domain, SSXRD, PR/SET domain ( H3K4 & H3K36 trimethyltransferase), and an array of C2H2

Zinc Finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...

domains (DNA binding).

History

In 1974 Jiri Forejt and P. Ivanyi identified a locus which they named Hst1 which controlled hybrid sterility. In 1982 a haplotype was identified controlling recombination rate ''wm7'', which would later be identified as PRDM9. In 1991 a protein binding to the minisatelite consensus sequence 5′-CCACCTGCCCACCTCT-3′ was detected and partially purified (named Msbp3 - minisatelite binding protein 3). This would later turn out to be the same PRDM9 protein independently identified later. In 2005 a gene was identified (named Meisetz) that is required for progression through meiotic prophase and has H3K4 methyltransferase activity. In 2009 Jiri Forejt and colleagues identified Hst1 as Meisetz/PRDM9 - the first and so far only speciation gene in mammals. Later in 2009 PRDM9 was identified as one of the fastest evolving genes in the genome. In 2010 three groups independently identified PRDM9 as controlling the positioning of recombination hotspots in humans and mice. in 2012 it was shown that almost all hotspots are positioned by PRDM9 and that in its absence hotspots form near promoters. In 2014 it was reported that the PRDM9 SET domain could also trimethylate H3K36 in vitro, which was confirmed in vivo in 2016. In 2016 it was shown that the hybrid sterility caused by PRDM9 can be reversed and that the sterility is caused by asymmetric double strand breaks.

Function in Recombination

PRDM9 mediates the process of meiosis by directing the sites of homologous recombination. In humans and mice, recombination does not occur evenly throughout the genome but at particular sites along the chromosomes called

s. Hotspots are regions of DNA about 1-2kb in length. There are approximately 30,000 to 50,000 hotspots within the human

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...

corresponding to one for every 50-100kb DNA on average. In humans, the average number of crossover recombination events per hotspot is one per 1,300 meioses, and the most extreme hotspot has a crossover frequency of one per 110 meioses. These hotspots are binding sites for the PRDM9 Zinc Finger array. Upon binding to DNA, PRDM9 catalyzes trimethylation of Histone 3 at lysine 4 and lysine 36. As a result, local nucleosomes are reorganized and through an unknown mechanism the recombination machinery is recruited to form double strand breaks.

Notes

References

External links