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PRDM9

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https://www.readbyqxmd.com/read/28820351/genomic-and-chromatin-features-shaping-meiotic-double-strand-break-formation-and-repair-in-mice
#1
Shintaro Yamada, Seoyoung Kim, Sam E Tischfield, Maria Jasin, Julian Lange, Scott Keeney
The SPO11-generated DNA double-strand breaks (DSBs) that initiate meiotic recombination occur non-randomly across genomes, but mechanisms shaping their distribution and repair remain incompletely understood. Here, we expand on recent studies of nucleotide-resolution DSB maps in mouse spermatocytes. We find that trimethylation of histone H3 lysine 36 around DSB hotspots is highly correlated, both spatially and quantitatively, with trimethylation of H3 lysine 4, consistent with coordinated formation and action of both PRDM9-dependent histone modifications...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28801461/structural-basis-of-human-prdm9-allele-c-specific-recognition-of-its-cognate-dna-sequence
#2
Anamika Patel, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng
PRDM9 is the only mammalian gene that has been associated with speciation. The PR/SET domain 9 (PRDM9) protein is a major determinant of meiotic recombination hotspots, and acts through sequence-specific DNA binding via its C2H2 zinc finger (ZF) tandem array, which is highly polymorphic within and between species. The most common human variant, PRDM9 allele A (PRDM9a), contains 13 fingers (ZF1-13). Allele C (PRDM9c) is the second-most common among African populations, and differs from PRDM9a by an arginine-to-serine change (R764S) in ZF9, and by replacement of ZF11 with two other fingers, yielding 14 fingers in PRDM9c...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28777546/site-selective-sensing-of-histone-methylation-enzyme-activity-via-an-arrayed-supramolecular-tandem-assay
#3
Yang Liu, Lizeth Perez, Adam D Gill, Magi Mettry, Lin Li, Yinsheng Wang, Richard J Hooley, Wenwan Zhong
Arrayed deep cavitands can be coupled to a fluorescence-based supramolecular tandem assay that allows site-selective in situ monitoring of post-translational modifications catalyzed by the lysine methyltransferase PRDM9 or the lysine demethylase JMJD2E. An arrayed sensor system containing only three cavitand components can detect the specific substrates of enzyme modification, in the presence of other histone peptides in the enzyme assay, enabling investigation of cross-reactivity over multiple methylation sites and interference from nonsubstrate peptides...
August 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28702511/variation-in-the-zinc-finger-of-prdm9-is-associated-with-the-absence-of-recombination-along-nondisjoined-chromosomes-21-of-maternal-origin
#4
Tiffany Renee Oliver, Candace Middlebrooks, Ariel Harden, Nyeisha Scott, Blair Johnson, Jillian Jones, Christin Walker, Corinthia Wilkerson, Sha-Hanna Saffold, Abisola Akinseye, Tunde Smith, Eleanor Feingold, Stephanie L Sherman
Variation in the zinc finger-binding domain (ZFBD) of the protein PR Domain-Containing Protein 9 (PRDM9) is associated with altered placement of recombination in the human genome. As both the absence and altered placement of recombination are observed among chromosomes 21 that nondisjoin, we genotyped the PRDM9 ZFBD among mothers of children with Trisomy 21 in efforts to determine if variation within this region is associated with the recombination-related risk for chromosome 21 nondisjunction (NDJ). In our approach, PCR was used to amplify the ZFBD of PRDM9 and products were then subjected to bi-directional Sanger sequencing...
December 2016: J Down Syndr Chromosom Abnorm
https://www.readbyqxmd.com/read/28676070/the-potential-of-shifting-recombination-hotspots-to-increase-genetic-gain-in-livestock-breeding
#5
Serap Gonen, Mara Battagin, Susan E Johnston, Gregor Gorjanc, John M Hickey
BACKGROUND: This study uses simulation to explore and quantify the potential effect of shifting recombination hotspots on genetic gain in livestock breeding programs. METHODS: We simulated three scenarios that differed in the locations of quantitative trait nucleotides (QTN) and recombination hotspots in the genome. In scenario 1, QTN were randomly distributed along the chromosomes and recombination was restricted to occur within specific genomic regions (i.e. recombination hotspots)...
July 4, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28590247/repeated-losses-of-prdm9-directed-recombination-despite-the-conservation-of-prdm9-across-vertebrates
#6
Zachary Baker, Molly Schumer, Yuki Haba, Lisa Bashkirova, Chris Holland, Gil G Rosenthal, Molly Przeworski
Studies of highly diverged species have revealed two mechanisms by which meiotic recombination is directed to the genome-through PRDM9 binding or by targeting promoter-like features-that lead to dramatically different evolutionary dynamics of hotspots. Here, we identify PRDM9 orthologs from genome and transcriptome data in 225 species. We find the complete PRDM9 ortholog across distantly related vertebrates but, despite this broad conservation, infer a minimum of six partial and three complete losses. Strikingly, taxa carrying the complete ortholog of PRDM9 are precisely those with rapid evolution of its predicted binding affinity, suggesting that all domains are necessary for directing recombination...
June 6, 2017: ELife
https://www.readbyqxmd.com/read/28527011/the-prdm9-krab-domain-is-required-for-meiosis-and-involved-in-protein-interactions
#7
Yukiko Imai, Frédéric Baudat, Miguel Taillepierre, Marcello Stanzione, Attila Toth, Bernard de Massy
PR domain-containing protein 9 (PRDM9) is a major regulator of the localization of meiotic recombination hotspots in the human and mouse genomes. This role involves its DNA-binding domain, which is composed of a tandem array of zinc fingers, and PRDM9-dependent trimethylation of histone H3 at lysine 4. PRDM9 is a member of the PRDM family of transcription regulators, but unlike other family members, it contains a Krüppel-associated box (KRAB)-related domain that is predicted to be a potential protein interaction domain...
May 19, 2017: Chromosoma
https://www.readbyqxmd.com/read/28374672/a-mutation-of-the-prdm9-mouse-hybrid-sterility-gene-carried-by-a-transgene
#8
O Mihola, Z Trachtulec
PRDM9 is a protein with histone-3-methyltransferase activity, which specifies the sites of meiotic recombination in mammals. Deficiency of the Prdm9 gene in the laboratory mouse results in complete arrest of the meiotic prophase of both sexes. Moreover, the combination of certain PRDM9 alleles from different mouse subspecies causes hybrid sterility, e.g., the male-specific meiotic arrest found in the (PWD/Ph × C57BL/6J)F1 animals. The fertility of all these mice can be rescued using a Prdm9-containing transgene...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28336543/in-vivo-binding-of-prdm9-reveals-interactions-with-noncanonical-genomic-sites
#9
Corinne Grey, Julie A J Clément, Jérôme Buard, Benjamin Leblanc, Ivo Gut, Marta Gut, Laurent Duret, Bernard de Massy
In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed an extensive analysis of PRDM9 binding in mouse spermatocytes. Unexpectedly, we identified a noncanonical recruitment of PRDM9 to sites that lack recombination activity and the PRDM9 binding consensus motif. These sites include gene promoters, where PRDM9 is recruited in a DSB-dependent manner...
April 2017: Genome Research
https://www.readbyqxmd.com/read/28292260/ruminant-specific-multiple-duplication-events-of-prdm9-before-speciation
#10
Abinash Padhi, Botong Shen, Jicai Jiang, Yang Zhou, George E Liu, Li Ma
BACKGROUND: Understanding the genetic and evolutionary mechanisms of speciation genes in sexually reproducing organisms would provide important insights into mammalian reproduction and fitness. PRDM9, a widely known speciation gene, has recently gained attention for its important role in meiotic recombination and hybrid incompatibility. Despite the fact that PRDM9 is a key regulator of recombination and plays a dominant role in hybrid incompatibility, little is known about the underlying genetic and evolutionary mechanisms that generated multiple copies of PRDM9 in many metazoan lineages...
March 14, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28155083/the-long-zinc-finger-domain-of-prdm9-forms-a-highly-stable-and-long-lived-complex-with-its-dna-recognition-sequence
#11
Yasmin Striedner, Theresa Schwarz, Thomas Welte, Andreas Futschik, Ulrich Rant, Irene Tiemann-Boege
PR domain containing protein 9 (PRDM9) is a meiosis-specific, multi-domain protein that regulates the location of recombination hotspots by targeting its DNA recognition sequence for double-strand breaks (DSBs). PRDM9 specifically recognizes DNA via its tandem array of zinc fingers (ZnFs), epigenetically marks the local chromatin by its histone methyltransferase activity, and is an important tether that brings the DNA into contact with the recombination initiation machinery. A strong correlation between PRDM9-ZnF variants and specific DNA motifs at recombination hotspots has been reported; however, the binding specificity and kinetics of the ZnF domain are still obscure...
June 2017: Chromosome Research
https://www.readbyqxmd.com/read/28126738/discovery-and-characterisation-of-the-automethylation-properties-of-prdm9
#12
Xiaoying Koh-Stenta, Anders Poulsen, Rong Li, John Liang Kuan Wee, Perlyn Zekui Kwek, Sin Yin Chew, Jianhe Peng, Liling Wu, Ernesto Guccione, Joma Joy, Jeffrey Hill
We have previously characterised the histone lysine methyltransferase properties of PRDM9, a member of the PRDM family of putative transcriptional regulators. PRDM9 displays broad substrate recognition and methylates a range of histone substrates, including octamers, core histone proteins, and peptides. In the present study, we show that PRDM9 performs intramolecular automethylation on multiple lysine residues localised to a lysine-rich region on the post-SET (suppressor of variegation 3-9, enhancer of zeste and trithorax) domain...
March 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28059126/an-exploratory-study-of-predisposing-genetic-factors-for-digeorge-velocardiofacial-syndrome
#13
Laia Vergés, Francesca Vidal, Esther Geán, Alexandra Alemany-Schmidt, Maria Oliver-Bonet, Joan Blanco
DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a disorder caused by a 22q11.2 deletion mediated by non-allelic homologous recombination (NAHR) between low-copy repeats (LCRs). We have evaluated the role of LCR22 genomic architecture and PRDM9 variants as DGS/VCFS predisposing factors. We applied FISH using fosmid probes on chromatin fibers to analyze the number of tandem repeat blocks in LCR22 in two DGS/VCFS fathers-of-origin with proven 22q11.2 NAHR susceptibility. Results revealed copy number variations (CNVs) of L9 and K3 fosmids in these individuals compared to controls...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27999113/the-composite-regulatory-basis-of-the-large-x-effect-in-mouse-speciation
#14
Erica L Larson, Sara Keeble, Dan Vanderpool, Matthew D Dean, Jeffrey M Good
The disruption of meiotic sex chromosome inactivation (MSCI) has been proposed to be a major developmental mechanism underlying the rapid evolution of hybrid male sterility. We tested this idea by analyzing cell-specific gene expression across spermatogenesis in two lineages of house mice and their sterile and fertile reciprocal hybrids. We found pervasive disruption of sex chromosome gene expression in sterile hybrids at every stage of spermatogenesis. Failure of MSCI was developmentally preceded by increased silencing of autosomal genes, supporting the hypothesis that divergence at the hybrid incompatibility gene, Prdm9, results in increased rates of autosomal asynapsis which in turn triggers widespread silencing of unsynapsed chromatin...
February 1, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27998939/a-pipeline-for-local-assembly-of-minisatellite-alleles-from-single-molecule-sequencing-data
#15
Denye Ogeh, Richard Badge
Motivation: The advent of Next Generation Sequencing (NGS) has led to the generation of enormous volumes of short read sequence data, cheaply and in reasonable time scales. Nevertheless, the quality of genome assemblies generated using NGS technologies has been greatly affected, compared to those generated using Sanger DNA sequencing. This is largely due to the inability of short read sequence data to scaffold repetitive structures, creating gaps, inversions and rearrangements and resulting in assemblies that are, at best, draft forms...
March 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/27932493/prdm9-interactions-with-other-proteins-provide-a-link-between-recombination-hotspots-and-the-chromosomal-axis-in-meiosis
#16
Emil D Parvanov, Hui Tian, Timothy Billings, Ruth L Saxl, Catrina Spruce, Rakesh Aithal, Lumir Krejci, Kenneth Paigen, Petko M Petkov
In mammals, meiotic recombination occurs at 1- to 2-kb genomic regions termed hotspots, whose positions and activities are determined by PRDM9, a DNA-binding histone methyltransferase. We show that the KRAB domain of PRDM9 forms complexes with additional proteins to allow hotspots to proceed into the next phase of recombination. By a combination of yeast-two hybrid assay, in vitro binding, and coimmunoprecipitation from mouse spermatocytes, we identified four proteins that directly interact with PRDM9's KRAB domain, namely CXXC1, EWSR1, EHMT2, and CDYL...
February 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27821479/functional-roles-of-acetylated-histone-marks-at-mouse-meiotic-recombination-hot-spots
#17
Irina V Getun, Zhen Wu, Mohammad Fallahi, Souad Ouizem, Qin Liu, Weimin Li, Roberta Costi, William R Roush, John L Cleveland, Philippe R J Bois
Meiotic recombination initiates following the formation of DNA double-strand breaks (DSBs) by the Spo11 endonuclease early in prophase I, at discrete regions in the genome coined "hot spots." In mammals, meiotic DSB site selection is directed in part by sequence-specific binding of PRDM9, a polymorphic histone H3 (H3K4Me3) methyltransferase. However, other chromatin features needed for meiotic hot spot specification are largely unknown. Here we show that the recombinogenic cores of active hot spots in mice harbor several histone H3 and H4 acetylation and methylation marks that are typical of open, active chromatin...
February 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27745971/the-landscape-of-mouse-meiotic-double-strand-break-formation-processing-and-repair
#18
Julian Lange, Shintaro Yamada, Sam E Tischfield, Jing Pan, Seoyoung Kim, Xuan Zhu, Nicholas D Socci, Maria Jasin, Scott Keeney
Heritability and genome stability are shaped by meiotic recombination, which is initiated via hundreds of DNA double-strand breaks (DSBs). The distribution of DSBs throughout the genome is not random, but mechanisms molding this landscape remain poorly understood. Here, we exploit genome-wide maps of mouse DSBs at unprecedented nucleotide resolution to uncover previously invisible spatial features of recombination. At fine scale, we reveal a stereotyped hotspot structure-DSBs occur within narrow zones between methylated nucleosomes-and identify relationships between SPO11, chromatin, and the histone methyltransferase PRDM9...
October 20, 2016: Cell
https://www.readbyqxmd.com/read/27744561/evolutionary-dynamics-of-meiotic-recombination-hotspots-regulator-prdm9-in-bovids
#19
Sonika Ahlawat, Sachinandan De, Priyanka Sharma, Rekha Sharma, Reena Arora, R S Kataria, T K Datta, R K Singh
Hybrid sterility or reproductive isolation in mammals has been attributed to allelic incompatibilities in a DNA-binding protein PRDM9. Not only is PRDM9 exceptional in being the only known 'speciation gene' in vertebrates, but it is also considered to be the fastest evolving gene in the genome. The terminal zinc finger (ZF) domain of PRDM9 specifies genome-wide meiotic recombination hotspot locations in mammals. Intriguingly, PRDM9 ZF domain is highly variable between as well as within species, possibly activating different recombination hotspots...
February 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/27733454/genome-wide-association-study-of-meiotic-recombination-phenotypes
#20
Ferdouse Begum, Reshmi Chowdhury, Vivian G Cheung, Stephanie L Sherman, Eleanor Feingold
Meiotic recombination is an essential step in gametogenesis, and is one that also generates genetic diversity. Genome-wide association studies (GWAS) and molecular studies have identified genes that influence of human meiotic recombination. RNF212 is associated with total or average number of recombination events, and PRDM9 is associated with the locations of hotspots, or sequences where crossing over appears to cluster. In addition, a common inversion on chromosome 17 is strongly associated with recombination...
December 7, 2016: G3: Genes—Genomes—Genetics
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