共查询到20条相似文献,搜索用时 15 毫秒
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Hondares E Rosell M Díaz-Delfín J Olmos Y Monsalve M Iglesias R Villarroya F Giralt M 《The Journal of biological chemistry》2011,286(50):43112-43122
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Julie Hanotel Nathalie Bessodes Aurore Thélie Marie Hedderich Karine Parain Benoit Van Driessche Karina De Oliveira Brandão Sadia Kricha Mette C. Jorgensen Anne Grapin-Botton Palle Serup Carine Van Lint Muriel Perron Tomas Pieler Kristine A. Henningfeld Eric J. Bellefroid 《Developmental biology》2014
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Timothy Billings Emil D Parvanov Christopher L Baker Michael Walker Kenneth Paigen Petko M Petkov 《Genome biology》2013,14(4):R35
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 Prdm9Cst and one activated by Prdm9Dom2, 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 Prdm9Cst activated hotspots. The binding specificity of each position in the Hlx1 binding site, activated by Prdm9Cst, 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. 相似文献16.
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Christopher L. Baker Shimpei Kajita Michael Walker Ruth L. Saxl Narayanan Raghupathy Kwangbom Choi Petko M. Petkov Kenneth Paigen 《PLoS genetics》2015,11(1)
Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured activity of the Prdm9
Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced experimentally. Comparing these two strains, we find that haplotype differences at hotspots lead to qualitative and quantitative changes in PRDM9 binding and activity. Using Mus spretus as an outlier, we found most variants affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing hotspot activity. Furthermore, M.m. castaneus×M.m. domesticus F1 hybrids exhibit novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin modification. These novel hotspots represent sites of historic evolutionary erosion that become activated in hybrids due to crosstalk between one parent''s Prdm9 allele and the opposite parent''s chromosome. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion. 相似文献
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