The long zinc finger domain of PRDM9 forms a highly stable and long-lived complex with its DNA recognition sequence

Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology
Yasmin StriednerIrene Tiemann-Boege

Abstract

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. Using two in vitro methods, gel mobility shift assays and switchSENSE, a quantitative biophysical approach that measures binding rates in real time, we determined that the PRDM9-ZnF domain forms a highly stable and long-lived complex with its recognition sequence, with a dissociation halftime of many hours. The ZnF domain exhibits an equilibrium dissociation constant (K D) in the nanomolar (nM) range, with polymorphisms in the recognition sequence directly affecting the binding affinity. We also determined that alternative sequences (15-16 nucleotides in length...Continue Reading

References

Dec 22, 1999·Journal of Molecular Endocrinology·T N CollingwoodA P Wolffe
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·S A WolfeC O Pabo
Feb 17, 2001·Current Opinion in Structural Biology·J H LaityP E Wright
Jun 29, 2002·Nature Genetics·Alec J Jeffreys, Rita Neumann
Jun 5, 2004·Nucleic Acids Research·Stephen E Halford, John F Marko
Jul 20, 2004·Nature Structural & Molecular Biology·Gu Li, Jonathan Widom
Dec 8, 2004·Nature Structural & Molecular Biology·Gu LiJonathan Widom
Apr 4, 2006·Cell Cycle·Katsuhiko Hayashi, Yasuhisa Matsui
Nov 15, 2008·Bioinformatics·Anton V PersikovMona Singh
Jul 28, 2009·Annual Review of Genomics and Human Genetics·Laurent Duret, Nicolas Galtier
Dec 10, 2009·PLoS Genetics·Peter L OliverChris P Ponting
Dec 31, 2009·PloS One·James H ThomasJay Shendure
Jan 2, 2010·Science·Emil D ParvanovKenneth Paigen
Feb 6, 2010·British Journal of Pharmacology·Edward C Hulme, Mike A Trevethick
Jul 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ingrid L BergAlec J Jeffreys
Mar 17, 2012·Science·Adam AutonGil McVean
Jun 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Levani ZandarashviliJunji Iwahara
Apr 27, 2013·Genome Biology·Timothy BillingsPetko M Petkov
Jul 11, 2013·Nature Communications·Andreas LangerUlrich Rant
Oct 8, 2013·Nucleic Acids Research·Anton V Persikov, Mona Singh
Oct 19, 2013·Nature Reviews. Genetics·F BaudatBernard de Massy
Mar 8, 2014·Genome Research·Christopher L BakerKenneth Paigen
Mar 19, 2014·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Masaru ItoKunihiro Ohta
Jul 9, 2014·Nature Communications·Jerrod J SchwartzJay Shendure
Nov 15, 2014·Science·Florencia PrattoR Daniel Camerini-Otero
Sep 15, 2015·PLoS Genetics·Christopher L BakerKenneth Paigen
Feb 3, 2016·Genes & Development·Anamika PatelXiaodong Cheng
Feb 4, 2016·Nature·Benjamin DaviesPeter Donnelly

Citations

Aug 31, 2018·PLoS Genetics·Corinne GreyBernard de Massy
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
Feb 1, 2020·Genes & Development·Catrina SpruceChristopher L Baker
Aug 13, 2017·The Journal of Biological Chemistry·Anamika PatelXiaodong Cheng
Jul 17, 2019·Life Science Alliance·Theresa SchwarzIrene Tiemann-Boege

Methods Mentioned

BETA
electrophoretic mobility shift
switchSENSE
NMR
immunoprecipitation
Affinity-Seq
PCR
Electrophoretic
chip
chips
Biosensors

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.

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.

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.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Nodding Syndrome

Nodding Syndrome is a neurological and epileptiform disorder characterized by psychomotor, mental, and growth retardation. Discover the latest research on Nodding Syndrome here.

LRRK2 & Microtubules

Mutations in the LRRK2 gene are risk-factors for developing Parkinson’s disease (PD). LRRK2 mutations in PD have been shown to enhance its association with microtubules. Here is the latest research.