Escape from X inactivation varies in mouse tissues.
Joel B. Berletch,Wenxiu Ma,Fan Yang,Jay Shendure,William Stafford Noble,Christine M. Disteche,Xinxian Deng +6 more
TLDR
Using a binomial model to assess allelic expression, a continuum between complete silencing and expression from the inactive X (Xi) is demonstrated, and common escape genes and genes with significant differences in XCI status between tissues were identified.Abstract:
X chromosome inactivation (XCI) silences most genes on one X chromosome in female mammals, but some genes escape XCI. To identify escape genes in vivo and to explore molecular mechanisms that regulate this process we analyzed the allele-specific expression and chromatin structure of X-linked genes in mouse tissues and cells with skewed XCI and distinguishable alleles based on single nucleotide polymorphisms. Using a binomial model to assess allelic expression, we demonstrate a continuum between complete silencing and expression from the inactive X (Xi). The validity of the RNA-seq approach was verified using RT-PCR with species-specific primers or Sanger sequencing. Both common escape genes and genes with significant differences in XCI status between tissues were identified. Such genes may be candidates for tissue-specific sex differences. Overall, few genes (3–7%) escape XCI in any of the mouse tissues examined, suggesting stringent silencing and escape controls. In contrast, an in vitro system represented by the embryonic-kidney-derived Patski cell line showed a higher density of escape genes (21%), representing both kidney-specific escape genes and cell-line specific escape genes. Allele-specific RNA polymerase II occupancy and DNase I hypersensitivity at the promoter of genes on the Xi correlated well with levels of escape, consistent with an open chromatin structure at escape genes. Allele-specific CTCF binding on the Xi clustered at escape genes and was denser in brain compared to the Patski cell line, possibly contributing to a more compartmentalized structure of the Xi and fewer escape genes in brain compared to the cell line where larger domains of escape were observed.read more
Citations
More filters
Journal ArticleDOI
Landscape of X chromosome inactivation across human tissues
Taru Tukiainen,Taru Tukiainen,Alexandra-Chloé Villani,Alexandra-Chloé Villani,Angela Yen,Angela Yen,Manuel A. Rivas,Manuel A. Rivas,Manuel A. Rivas,Jamie L. Marshall,Jamie L. Marshall,Rahul Satija,Rahul Satija,Matthew Aguirre,Matthew Aguirre,Laura D. Gauthier,Laura D. Gauthier,Mark Fleharty,Andrew Kirby,Andrew Kirby,Beryl B. Cummings,Beryl B. Cummings,Stephane E. Castel,Konrad J. Karczewski,Konrad J. Karczewski,François Aguet,Andrea Byrnes,Andrea Byrnes,Tuuli Lappalainen,Aviv Regev,Aviv Regev,Kristin G. Ardlie,Nir Hacohen,Nir Hacohen,Daniel G. MacArthur,Daniel G. MacArthur +35 more
TL;DR: It is shown that incomplete XCI affects at least 23% of X-chromosomal genes, identified seven genes that escape XCI with support from multiple lines of evidence and demonstrated that escape from XCI results in sex biases in gene expression, establishing incomplete X CI as a mechanism that is likely to introduce phenotypic diversity.
Control of Cell Identity Genes Occurs in Insulated Neighborhoods in Mammalian Chromosomes
Jill M. Dowen,Zi Peng Fan,Denes Hnisz,Gang Ren,Brian J. Abraham,Abraham S. Weintraub,Jurian Schuijers,Tong Ihn Lee,Keji Zhao,Lyndon Nuoxi Zhang,Richard A. Young +10 more
TL;DR: In this article, the authors used ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by co-hesin.
Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators
Jennifer F. Hughes,Helen Skaletsky,Laura G. Brown,Tatyana Pyntikova,Ting-Jan Cho,Natalia Koutseva,Sara Zaghlul,Tina Graves,Susie Rock,Colin Kremitzki,Robert S. Fulton,Shannon Dugan,Yan Ding,Donna Morton,Ziad Khan,Lora Lewis,Christian J. Buhay,Qiaoyan Wang,Jennifer Watt,Michael Holder,Sandy Lee,Lynne V. Nazareth,Jessica Alföldi,Steve Rozen,Donna M. Muzny,Wesley C. Warren,Richard A. Gibbs,Rick K. Wilson,Daniel W. Bellott,David C. Page +29 more
TL;DR: This article reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes, and concluded that the gene content of Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability.
Journal ArticleDOI
Structural organization of the inactive X chromosome in the mouse
Luca Giorgetti,Luca Giorgetti,Bryan R. Lajoie,Ava C. Carter,Mikael Attia,Ye Zhan,Jin Xu,Chong-Jian Chen,Noam Kaplan,Howard Y. Chang,Edith Heard,Edith Heard,Job Dekker +12 more
TL;DR: A crucial role is demonstrated for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC–seq) and RNA sequencing, and deletion of the boundary disrupts mega-domain formation.
Journal ArticleDOI
Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias
Andrew Dunford,David M. Weinstock,David M. Weinstock,Virginia Savova,Steven E. Schumacher,Steven E. Schumacher,John P Cleary,Akinori Yoda,Timothy J. Sullivan,Julian M. Hess,Alexander A. Gimelbrant,Alexander A. Gimelbrant,Rameen Beroukhim,Rameen Beroukhim,Michael S. Lawrence,Gad Getz,Gad Getz,Andrew A. Lane,Andrew A. Lane +18 more
TL;DR: It is concluded that biallelic expression of EXITS genes in females explains a portion of the reduced cancer incidence in females as compared to males across a variety of tumor types.
References
More filters
Journal ArticleDOI
Fast and accurate short read alignment with Burrows–Wheeler transform
Heng Li,Richard Durbin +1 more
TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Journal ArticleDOI
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome
TL;DR: Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches and can be used simultaneously to achieve even greater alignment speeds.
Journal ArticleDOI
Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation
Cole Trapnell,Cole Trapnell,Brian A. Williams,Geo Pertea,Ali Mortazavi,Gordon Kwan,Marijke J. van Baren,Steven L. Salzberg,Barbara J. Wold,Lior Pachter +9 more
TL;DR: The results suggest that Cufflinks can illuminate the substantial regulatory flexibility and complexity in even this well-studied model of muscle development and that it can improve transcriptome-based genome annotation.
Journal ArticleDOI
Model-based Analysis of ChIP-Seq (MACS)
Yong Zhang,Tao Liu,Clifford A. Meyer,Jérôme Eeckhoute,David S. Johnson,Bradley E. Bernstein,Bradley E. Bernstein,Chad Nusbaum,Richard M. Myers,Myles Brown,Wei Li,X. Shirley Liu +11 more
TL;DR: This work presents Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer, and uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions.
Journal ArticleDOI
Initial sequencing and comparative analysis of the mouse genome.
Robert H. Waterston,Kerstin Lindblad-Toh,Ewan Birney,Jane Rogers,Josep F. Abril,Pankaj K. Agarwal,Richa Agarwala,Rachel Ainscough,Marina Alexandersson,Peter An,Stylianos E. Antonarakis,John Attwood,Robert Baertsch,J Bailey,K F Barlow,Stephan Beck,Eric Berry,Bruce W. Birren,Toby Bloom,Peer Bork,Marc Botcherby,Nicolas Bray,Michael R. Brent,Daniel G. Brown,Daniel G. Brown,Stephen D. Brown,Carol J. Bult,John Burton,Jonathan Butler,R. D. Campbell,Piero Carninci,Simon Cawley,Francesca Chiaromonte,Asif T. Chinwalla,Deanna M. Church,Michele Clamp,C M Clee,Francis S. Collins,Lisa Cook,Richard R. Copley,Alan Coulson,Olivier Couronne,James Cuff,Val Curwen,Tim Cutts,Mark J. Daly,Robert David,Joy Davies,Kimberly D. Delehaunty,Justin Deri,Emmanouil T. Dermitzakis,Colin N. Dewey,Nicholas J. Dickens,Mark Diekhans,Sheila Dodge,Inna Dubchak,Diane M. Dunn,Sean R. Eddy,Laura Elnitski,Richard D. Emes,Pallavi Eswara,Eduardo Eyras,Adam Felsenfeld,Ginger A. Fewell,Paul Flicek,Karen Foley,Wayne N. Frankel,Lucinda Fulton,Robert S. Fulton,Terrence S. Furey,Diane Gage,Richard A. Gibbs,Gustavo Glusman,Sante Gnerre,Nick Goldman,Leo Goodstadt,Darren Grafham,Tina Graves,Eric D. Green,Simon G. Gregory,Roderic Guigó,Mark S. Guyer,Ross C. Hardison,David Haussler,Yoshihide Hayashizaki,Deana W. LaHillier,Angela S. Hinrichs,Wratko Hlavina,Timothy Holzer,Fan Hsu,Axin Hua,Tim Hubbard,Adrienne Hunt,Ian J. Jackson,David B. Jaffe,L. Steven Johnson,Matthew Jones,Thomas A. Jones,A Joy,Michael Kamal,Elinor K. Karlsson,Donna Karolchik,Arkadiusz Kasprzyk,Jun Kawai,Evan Keibler,Cristyn Kells,W. James Kent,Andrew Kirby,Diana L. Kolbe,Ian F Korf,Raju Kucherlapati,Edward J. Kulbokas,David Kulp,Tom Landers,J. P. Leger,Steven Leonard,Ivica Letunic,Rosie Levine,Jia Li,Ming Li,Christine Lloyd,Susan Lucas,Bin Ma,Donna Maglott,Elaine R. Mardis,Lucy Matthews,Evan Mauceli,John Mayer,Megan McCarthy,W. Richard McCombie,Stuart McLaren,Kirsten McLay,John Douglas Mcpherson,James Meldrim,Beverley Meredith,Jill P. Mesirov,Webb Miller,Tracie L. Miner,Emmanuel Mongin,Kate Montgomery,Michael J. Morgan,Richard Mott,James C. Mullikin,Donna M. Muzny,William E. Nash,Joanne O. Nelson,Michael N. Nhan,Robert Nicol,Zemin Ning,Chad Nusbaum,Michael J. O’Connor,Yasushi Okazaki,Karen Oliver,Emma Overton-Larty,Lior Pachter,Genís Parra,Kymberlie H. Pepin,Jane Peterson,Pavel A. Pevzner,Robert W. Plumb,Craig Pohl,Alex Poliakov,Tracy C. Ponce,Chris P. Ponting,Simon C. Potter,Michael A. Quail,Alexandre Reymond,Bruce A. Roe,Krishna M. Roskin,Edward M. Rubin,Alistair G. Rust,Ralph Santos,Victor Sapojnikov,Brian Schultz,Jörg Schultz,Matthias S. Schwartz,Scott Schwartz,Carol Scott,Steven Seaman,Steve Searle,Ted Sharpe,Andrew Sheridan,Ratna Shownkeen,Sarah Sims,Jonathan Singer,Guy Slater,Arian F.A. Smit,Douglas Smith,Brian Spencer,Arne Stabenau,Nicole Stange-Thomann,Charles W. Sugnet,Mikita Suyama,Glenn Tesler,Johanna Thompson,David Torrents,Evanne Trevaskis,John Tromp,Catherine Ucla,Abel Ureta-Vidal,Jade P. Vinson,Andrew von Niederhausern,Claire M. Wade,Melanie M. Wall,R. J. Weber,Robert B. Weiss,Michael C. Wendl,Anthony P. West,Kris A. Wetterstrand,Raymond Wheeler,Simon Whelan,Jamey Wierzbowski,David Willey,Sophie Williams,Richard K. Wilson,Eitan E. Winter,Kim C. Worley,Dudley Wyman,Shan Yang,Shiaw Pyng Yang,Evgeny M. Zdobnov,Michael C. Zody,Eric S. Lander +222 more
TL;DR: The results of an international collaboration to produce a high-quality draft sequence of the mouse genome are reported and an initial comparative analysis of the Mouse and human genomes is presented, describing some of the insights that can be gleaned from the two sequences.
Related Papers (5)
X-inactivation profile reveals extensive variability in X-linked gene expression in females
Landscape of X chromosome inactivation across human tissues
Taru Tukiainen,Taru Tukiainen,Alexandra-Chloé Villani,Alexandra-Chloé Villani,Angela Yen,Angela Yen,Manuel A. Rivas,Manuel A. Rivas,Manuel A. Rivas,Jamie L. Marshall,Jamie L. Marshall,Rahul Satija,Rahul Satija,Matthew Aguirre,Matthew Aguirre,Laura D. Gauthier,Laura D. Gauthier,Mark Fleharty,Andrew Kirby,Andrew Kirby,Beryl B. Cummings,Beryl B. Cummings,Stephane E. Castel,Konrad J. Karczewski,Konrad J. Karczewski,François Aguet,Andrea Byrnes,Andrea Byrnes,Tuuli Lappalainen,Aviv Regev,Aviv Regev,Kristin G. Ardlie,Nir Hacohen,Nir Hacohen,Daniel G. MacArthur,Daniel G. MacArthur +35 more
Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators
Daniel W. Bellott,Jennifer F. Hughes,Helen Skaletsky,Laura G. Brown,Tatyana Pyntikova,Ting-Jan Cho,Natalia Koutseva,Sara Zaghlul,Tina Graves,Susie Rock,Colin Kremitzki,Robert S. Fulton,Shannon Dugan,Yan Ding,Donna Morton,Ziad Khan,Lora Lewis,Christian J. Buhay,Qiaoyan Wang,Jennifer Watt,Michael Holder,Sandy Lee,Lynne V. Nazareth,Jessica Alföldi,Steve Rozen,Donna M. Muzny,Wesley C. Warren,Richard A. Gibbs,Richard K. Wilson,David C. Page +29 more