Genetic compensation: A phenomenon in search of mechanisms.
TLDR
This review revisits studies reporting genetic compensation in higher eukaryotes and outlines possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.Abstract:
Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969. Since then, genetic compensation has been documented many times in a number of model organisms; however, our understanding of the underlying molecular mechanisms remains limited. In this review, we revisit studies reporting genetic compensation in higher eukaryotes and outline possible molecular mechanisms, which may include both transcriptional and posttranscriptional processes.read more
Citations
More filters
Journal Article
Genetic compensation induced by deleterious mutations but not gene knockdowns
TL;DR: In this article, the authors show that egfl7 mutants do not show any obvious phenotypes while animals injected with egfl 7 morpholino (morphants) exhibit severe vascular defects, indicating that the activation of a compensatory network to buffer against deleterious mutations was not observed after translational or transcriptional knockdown.
Journal ArticleDOI
Genetic compensation triggered by mutant mRNA degradation
Mohamed A. El-Brolosy,Zacharias Kontarakis,Andrea Rossi,Andrea Rossi,Carsten Kuenne,Stefan Günther,Nana Fukuda,Khrievono Kikhi,Giulia L. M. Boezio,Carter M. Takacs,Carter M. Takacs,Shih-Lei Lai,Shih-Lei Lai,Ryuichi Fukuda,Claudia Gerri,Claudia Gerri,Antonio J. Giraldez,Didier Y.R. Stainier +17 more
TL;DR: Transcriptional adaptation, a genetic compensation process by which organisms respond to mutations by upregulating related genes, is triggered by mRNA decay and involves a sequence-dependent mechanism.
Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA
Schraga Schwartz,Douglas A. Bernstein,Maxwell R. Mumbach,Marko Jovanovic,Rebecca H. Herbst,Brian X. León-Ricardo,Jesse M. Engreitz,Mitchell Guttman,Rahul Satija,Eric S. Lander,Gerald R. Fink,Aviv Regev,Aviv Regev,Aviv Regev +13 more
TL;DR: This work identifies an enhanced, transcriptome-wide scope for pseudouridine and methods to dissect its underlying mechanisms and function and discovers hundreds of unique sites in human and yeast mRNAs and snoRNAs.
Journal ArticleDOI
IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?
John B. Allard,Cunming Duan +1 more
TL;DR: The emerging explanation that many IGFBP functions have evolved to allow the targeted adjustment of IGF signaling under stressful or irregular conditions, which would likely not be revealed in a standard laboratory setting are explored.
Journal ArticleDOI
Highly Efficient CRISPR-Cas9-Based Methods for Generating Deletion Mutations and F0 Embryos that Lack Gene Function in Zebrafish
Kazuyuki Hoshijima,Michael J. Jurynec,Dana Klatt Shaw,Ashley M. Jacobi,Mark A. Behlke,David Grunwald +5 more
TL;DR: Supernumerary guanine nucleotides at the 5' ends of single guide RNAs (sgRNAs) account for diminished CRISPR-Cas9 activity in zebrafish embryos and heritable deletion mutations of at least 50 kbp can be readily induced using pairs of duplex guide RNPs targeted to a single chromosome.
References
More filters
Journal ArticleDOI
A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog
Astrid Hagelkruys,Sabine Lagger,Julia Krahmer,Alexandra Leopoldi,Matthias Artaker,Oliver Pusch,Jürgen Zezula,Simon Weissmann,Yunli Xie,Christian Schöfer,Michaela Schlederer,Gerald Brosch,Patrick Matthias,Jim Selfridge,Hans Lassmann,Jürgen A. Knoblich,Christian Seiser +16 more
TL;DR: The data indicate that HDAC1 and HDAC2 have a common function in maintaining proper chromatin structures and show that Hdac2 has a unique role by controlling the fate of neural progenitors during normal brain development.
Journal ArticleDOI
The histone code regulating expression of the imprinted mouse Igf2r gene.
TL;DR: A model of the histone code for Igf2r, and Air imprinting is proposed that defines histone modifications specific for the putative gametic imprint DMR2, and explains the tissue-specific imprinting of Igf 2r in the mouse and the absence of IGF2R imprinting in human.
Journal ArticleDOI
Allele-specific histone modifications regulate expression of the Dlk1-Gtl2 imprinted domain
TL;DR: Interactions between DNA methylation and histone acetylation are involved in regulating the imprinting of the Dlk1-Gtl2 locus, and further analysis of these animals shows that the loss of allele-specific methylation is accompanied by increased paternal histone methylation at the Gtl2 DMR.
Journal ArticleDOI
9 Mechanism of Translation Initiation in the Yeast Saccharomyces cerevisiae
TL;DR: Genetic and biochemical analysis of the yeast Saccharomyces cerevisiae is helping to elucidate molecular mechanisms in the translation initiation pathway, and genetic studies in yeast provide the best opportunity to establish the physiological relevance of conclusions reached using cell-free systems.
Journal ArticleDOI
A specific role for cyclin D1 in mammary gland development.
TL;DR: Cyclin D1 seems to play a critical role in pregnancy-induced proliferation of mammary epithelium and participates in neoplasia, as the majority of human mammary carcinomas contain elevated levels of this cyclin.
Related Papers (5)
Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system
The zebrafish reference genome sequence and its relationship to the human genome.
Kerstin Howe,Matthew D. Clark,Carlos Torroja,Carlos Torroja,James Torrance,Camille Berthelot,Matthieu Muffato,John E. Collins,Sean Humphray,Karen McLaren,Lucy Matthews,Stuart McLaren,Ian M Sealy,Mario Caccamo,Carol Churcher,Carol Scott,Jeffrey C. Barrett,Romke Koch,Gerd Jörg Rauch,Simon D. M. White,William Chow,Britt Kilian,Leonor T. Quintais,José Afonso Guerra-Assunção,Yi Zhou,Yong Gu,Jennifer Yen,Jan Hinnerk Vogel,Tina Eyre,Seth Redmond,Ruby Banerjee,Jianxiang Chi,Beiyuan Fu,Elizabeth Langley,Sean Maguire,Gavin K. Laird,D. M. Lloyd,Emma J. Kenyon,Sarah Donaldson,Harminder Sehra,Jeff Almeida-King,Jane E. Loveland,Stephen J. Trevanion,Matthew Jones,Michael A. Quail,Dave Willey,Adrienne Hunt,John Burton,Sarah Sims,Kirsten McLay,Bob Plumb,J. C. Davis,Chris Clee,Karen Oliver,Richard M. Clark,Clare Riddle,David Eliott,Glen Threadgold,Glenn Harden,Darren Ware,Beverly Mortimer,Giselle Kerry,Paul Heath,Benjamin Phillimore,Alan Tracey,N Corby,Matthew Dunn,Christopher M. Johnson,Jonathan Wood,Susan J. Clark,Sarah Pelan,Guy Griffiths,Michelle Smith,Rebecca Glithero,Philip Howden,Nick Barker,Christopher Stevens,Joanna Harley,Karen Holt,Georgios Panagiotidis,J Lovell,Helen Beasley,Carl Henderson,Daria Gordon,Katherine Auger,Debbie E. Wright,Joanna Collins,Claire Raisen,Lauren Dyer,Kenric Leung,Lauren Robertson,Kirsty Ambridge,Daniel Leongamornlert,Sarah McGuire,Ruth Gilderthorp,C Griffiths,Deepa Manthravadi,Sarah Nichol,Gary L A Barker,S. Whitehead,Michael Kay,Jacqueline Brown,Clare Murnane,Emma Gray,Matthew Humphries,N Sycamore,Darren Barker,David S. Saunders,J. M. Wallis,A K Babbage,S Hammond,M Mashreghi-Mohammadi,Lucy Barr,Sancha Martin,Paul Wray,Andrew D. Ellington,Nicholas Matthews,Matthew Ellwood,Rebecca Woodmansey,Graham Clark,James D. Cooper,A Tromans,Darren Grafham,C. D. Skuce,Richard Pandian,Robert Andrews,Elliot Harrison,A M Kimberley,J Garnett,Nigel Fosker,Rebekah Hall,P Garner,Daniel P. Kelly,Christine P. Bird,Sophie Palmer,Ines Gehring,Andrea Berger,Christopher M. Dooley,Christopher M. Dooley,Zübeyde Ersan-Ürün,Cigdem Eser,Horst Geiger,Maria Geisler,Lena Karotki,Anette Kirn,Judith Konantz,Martina Konantz,Martina Oberländer,Silke Rudolph-Geiger,Mathias Teucke,Kazutoyo Osoegawa,Baoli Zhu,Amanda Rapp,Sara Widaa,Cordelia Langford,Fengtang Yang,Nigel P. Carter,Jennifer Harrow,Zemin Ning,Javier Herrero,Steve Searle,Anton J. Enright,Robert Geisler,Robert Geisler,Ronald H.A. Plasterk,Charles Lee,Monte Westerfield,Pieter J. de Jong,Leonard I. Zon,John H. Postlethwait,Christiane Nüsslein-Volhard,Tim Hubbard,Hugues Roest Crollius,Jane Rogers,Derek L. Stemple +174 more