Affinity-seq detects genome-wide PRDM9 binding sites and reveals the impact of prior chromatin modifications on mammalian recombination hotspot usage

Epigenetics & Chromatin
Michael WalkerPetko M Petkov

Abstract

Genetic recombination plays an important role in evolution, facilitating the creation of new, favorable combinations of alleles and the removal of deleterious mutations by unlinking them from surrounding sequences. In most mammals, the placement of genetic crossovers is determined by the binding of PRDM9, a highly polymorphic protein with a long zinc finger array, to its cognate binding sites. It is one of over 800 genes encoding proteins with zinc finger domains in the human genome. We report a novel technique, Affinity-seq, that for the first time identifies both the genome-wide binding sites of DNA-binding proteins and quantitates their relative affinities. We have applied this in vitro technique to PRDM9, the zinc-finger protein that activates genetic recombination, obtaining new information on the regulation of hotspots, whose locations and activities determine the recombination landscape. We identified 31,770 binding sites in the mouse genome for the PRDM9(Dom2) variant. Comparing these results with hotspot usage in vivo, we find that less than half of potential PRDM9 binding sites are utilized in vivo. We show that hotspot usage is increased in actively transcribed genes and decreased in genomic regions containing H3K9me...Continue Reading

References

Aug 11, 1991·Nucleic Acids Research·S Karlin, C Macken
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·A BoultonR J Redfield
Oct 2, 2003·Genome Biology·Raul Urrutia
Aug 27, 2005·Cell·Dmitry K PokholokRichard A Young
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Piotr A MieczkowskiThomas D Petes
Jun 11, 2008·Molecular and Cellular Biology·Michael L YoudellJane Mellor
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jan 2, 2010·Science·Emil D ParvanovKenneth Paigen
Jan 30, 2010·Bioinformatics·Aaron R Quinlan, Ira M Hall
Feb 20, 2010·Nature Reviews. Genetics·Kenneth Paigen, Petko Petkov
Oct 5, 2010·PLoS Genetics·Robert S IllingworthAdrian P Bird
Jan 5, 2011·Nature Chemical Biology·Beat FierzTom W Muir
Feb 18, 2011·Bioinformatics·Qiang Song, Andrew D Smith
Jul 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ingrid L BergAlec J Jeffreys
Jul 22, 2011·Nature·Anjali G HinchSimon R Myers
Nov 8, 2011·Genes & Development·Kiran BattaB Franklin Pugh
Mar 17, 2012·Science·Adam AutonGil McVean
Jul 31, 2012·PLoS Genetics·Cynthia SandorMichel Georges
Aug 28, 2012·Nature Structural & Molecular Biology·Michaela SmolleJerry L Workman
Jan 15, 2013·Current Opinion in Genetics & Development·Valérie Borde, Bernard de Massy
Mar 7, 2013·Nature Structural & Molecular Biology·Gabriel E Zentner, Steven Henikoff
Apr 25, 2013·PloS One·Cynthia C Steiner, Oliver A Ryder
Apr 27, 2013·Genome Biology·Timothy BillingsPetko M Petkov
Oct 19, 2013·Nature Reviews. Genetics·Frédéric BaudatBernard de Massy
Jan 23, 2014·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Hiromitsu KonoToshihiko Shiroishi
Mar 8, 2014·Genome Research·Christopher L BakerKenneth Paigen
Mar 19, 2014·The Journal of Biological Chemistry·Mohammad S EramMasoud Vedadi
Jul 9, 2014·Nature Communications·Jerrod J SchwartzJay Shendure

❮ Previous
Next ❯

Citations

Nov 29, 2015·Human Molecular Genetics·Morten HillmerHildegard Kehrer-Sawatzki
Nov 11, 2017·Nucleic Acids Research·So MaezawaSatoshi H Namekawa
Aug 31, 2018·PLoS Genetics·Corinne GreyBernard de Massy
Oct 21, 2018·Genome Research·Armande Ang HoulePhilip Awadalla
Dec 30, 2018·Genetics·Christopher L BakerKenneth Paigen
Nov 8, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Isabel AlvesPhilip Awadalla
Nov 8, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Irene Tiemann-BoegeAngelika Heissl
Oct 1, 2019·FEBS Letters·Nathan PalmerPhilipp Kaldis
Feb 1, 2020·Genes & Development·Catrina SpruceChristopher L Baker
Aug 25, 2019·Nature Communications·Kwan-Wood Gabriel LamR Daniel Camerini-Otero
Feb 20, 2019·Nature Structural & Molecular Biology·Lucas PatelKevin D Corbett
Jul 17, 2019·Life Science Alliance·Theresa SchwarzIrene Tiemann-Boege
Feb 6, 2017·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Yasmin StriednerIrene Tiemann-Boege
Jun 9, 2017·Genetics·Andrew P MorganFernando Pardo-Manuel de Villena
Apr 21, 2018·Genetics·Sarah Thibault-SennettGalina V Petukhova
Feb 14, 2020·Nature Communications·Jacob PaianoAndré Nussenzweig
Sep 7, 2018·Nature·Kevin BrickGalina V Petukhova
Aug 21, 2020·Genetics·Samuel J WidmayerDavid L Aylor
Sep 1, 2020·Molecular Human Reproduction·Zheng-Hui ZhaoQing-Yuan Sun
Oct 25, 2020·Science Advances·Natalie R PowersTanmoy Bhattacharyya
Jan 26, 2018·Trends in Genetics : TIG·Kenneth Paigen, Petko M Petkov
May 7, 2021·Genetics·Samuel J WidmayerDavid L Aylor
Jul 15, 2021·Cell·Florencia PrattoR Daniel Camerini-Otero

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE52628
GSE61613

Methods Mentioned

BETA
Affinity-seq
ChIP-seq
RNA-seq
ChIP
histone acetylation
DNA-seq

Software Mentioned

Illumina ® Casava
BowTie
BWA
RSEM
samtools
- JDK
SAM Spec
MEME Suite
BioJava
mathop

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.