DNA binding specificities of the long zinc-finger recombination protein PRDM9

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Publikace nespadá pod Filozofickou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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BILLINGS Timothy PARVANOV Emil Damyanov BAKER Christopher L. WALKER Michael PAIGEN Kenneth PETKOV Petko M.

Rok publikování 2013
Druh Článek v odborném periodiku
Časopis / Zdroj Genome Biology
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-4-r35
Doi http://dx.doi.org/10.1186/gb-2013-14-4-r35
Klíčová slova recombination hotspots; PRDM9; DNA binding; EMSA; zinc-finger proteins
Popis Background: Meiotic recombination ensures proper segregation of homologous chromosomes and creates genetic variation. In many organisms, recombination occurs at limited sites, termed 'hotspots', whose positions in mammals are determined by PR domain member 9 (PRDM9), a long-array zinc-finger and chromatin-modifier protein. Determining the rules governing the DNA binding of PRDM9 is a major issue in understanding how it functions. Results: Mouse PRDM9 protein variants bind to hotspot DNA sequences in a manner that is specific for both PRDM9 and DNA haplotypes, and that in vitro binding parallels its in vivo biological activity. Examining four hotspots, three activated by Prdm9(Cst) and one activated by Prdm9(Dom2), we found that all binding sites required the full array of 11 or 12 contiguous fingers, depending on the allele, and that there was little sequence similarity between the binding sites of the three Prdm9(Cst) activated hotspots. The binding specificity of each position in the Hlx1 binding site, activated by Prdm9(Cst), was tested by mutating each nucleotide to its three alternatives. The 31 positions along the binding site varied considerably in the ability of alternative bases to support binding, which also implicates a role for additional binding to the DNA phosphate backbone. Conclusions: These results, which provide the first detailed mapping of PRDM9 binding to DNA and, to our knowledge, the most detailed analysis yet of DNA binding by a long zinc-finger array, make clear that the binding specificities of PRDM9, and possibly other long-array zinc-finger proteins, are unusually complex.
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