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Jesse R. Dixon

Bio: Jesse R. Dixon is an academic researcher from Salk Institute for Biological Studies. The author has contributed to research in topics: Chromatin & Genome. The author has an hindex of 23, co-authored 45 publications receiving 15663 citations. Previous affiliations of Jesse R. Dixon include Howard Hughes Medical Institute & University of California, San Diego.


Papers
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Journal ArticleDOI
17 May 2012-Nature
TL;DR: It is found that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
Abstract: The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories, and numerous models have been proposed for how chromosomes fold within chromosome territories. These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid advances in the study of three-dimensional genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide. Here we investigate the three-dimensional organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. Finally, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.

5,774 citations

Journal ArticleDOI
Anshul Kundaje1, Wouter Meuleman1, Wouter Meuleman2, Jason Ernst3, Misha Bilenky4, Angela Yen2, Angela Yen1, Alireza Heravi-Moussavi4, Pouya Kheradpour1, Pouya Kheradpour2, Zhizhuo Zhang2, Zhizhuo Zhang1, Jianrong Wang2, Jianrong Wang1, Michael J. Ziller2, Viren Amin5, John W. Whitaker, Matthew D. Schultz6, Lucas D. Ward2, Lucas D. Ward1, Abhishek Sarkar1, Abhishek Sarkar2, Gerald Quon2, Gerald Quon1, Richard Sandstrom7, Matthew L. Eaton1, Matthew L. Eaton2, Yi-Chieh Wu2, Yi-Chieh Wu1, Andreas R. Pfenning1, Andreas R. Pfenning2, Xinchen Wang1, Xinchen Wang2, Melina Claussnitzer2, Melina Claussnitzer1, Yaping Liu1, Yaping Liu2, Cristian Coarfa5, R. Alan Harris5, Noam Shoresh2, Charles B. Epstein2, Elizabeta Gjoneska1, Elizabeta Gjoneska2, Danny Leung8, Wei Xie8, R. David Hawkins8, Ryan Lister6, Chibo Hong9, Philippe Gascard9, Andrew J. Mungall4, Richard A. Moore4, Eric Chuah4, Angela Tam4, Theresa K. Canfield7, R. Scott Hansen7, Rajinder Kaul7, Peter J. Sabo7, Mukul S. Bansal10, Mukul S. Bansal2, Mukul S. Bansal1, Annaick Carles4, Jesse R. Dixon8, Kai How Farh2, Soheil Feizi1, Soheil Feizi2, Rosa Karlic11, Ah Ram Kim2, Ah Ram Kim1, Ashwinikumar Kulkarni12, Daofeng Li13, Rebecca F. Lowdon13, Ginell Elliott13, Tim R. Mercer14, Shane Neph7, Vitor Onuchic5, Paz Polak15, Paz Polak2, Nisha Rajagopal8, Pradipta R. Ray12, Richard C Sallari1, Richard C Sallari2, Kyle Siebenthall7, Nicholas A Sinnott-Armstrong1, Nicholas A Sinnott-Armstrong2, Michael Stevens13, Robert E. Thurman7, Jie Wu16, Bo Zhang13, Xin Zhou13, Arthur E. Beaudet5, Laurie A. Boyer1, Philip L. De Jager2, Philip L. De Jager15, Peggy J. Farnham17, Susan J. Fisher9, David Haussler18, Steven J.M. Jones19, Steven J.M. Jones4, Wei Li5, Marco A. Marra4, Michael T. McManus9, Shamil R. Sunyaev15, Shamil R. Sunyaev2, James A. Thomson20, Thea D. Tlsty9, Li-Huei Tsai1, Li-Huei Tsai2, Wei Wang, Robert A. Waterland5, Michael Q. Zhang21, Lisa Helbling Chadwick22, Bradley E. Bernstein6, Bradley E. Bernstein2, Bradley E. Bernstein15, Joseph F. Costello9, Joseph R. Ecker11, Martin Hirst4, Alexander Meissner2, Aleksandar Milosavljevic5, Bing Ren8, John A. Stamatoyannopoulos7, Ting Wang13, Manolis Kellis2, Manolis Kellis1 
19 Feb 2015-Nature
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

5,037 citations

Journal ArticleDOI
19 Feb 2015-Nature
TL;DR: Mapping genome-wide chromatin interactions in human embryonic stem cells and four human ES-cell-derived lineages reveals extensive chromatin reorganization during lineage specification, providing a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.
Abstract: Higher-order chromatin structure is emerging as an important regulator of gene expression. Although dynamic chromatin structures have been identified in the genome, the full scope of chromatin dynamics during mammalian development and lineage specification remains to be determined. By mapping genome-wide chromatin interactions in human embryonic stem (ES) cells and four human ES-cell-derived lineages, we uncover extensive chromatin reorganization during lineage specification. We observe that although self-associating chromatin domains are stable during differentiation, chromatin interactions both within and between domains change in a striking manner, altering 36% of active and inactive chromosomal compartments throughout the genome. By integrating chromatin interaction maps with haplotype-resolved epigenome and transcriptome data sets, we find widespread allelic bias in gene expression correlated with allele-biased chromatin states of linked promoters and distal enhancers. Our results therefore provide a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.

1,393 citations

Journal ArticleDOI
02 Aug 2012-Nature
TL;DR: It is shown that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters, which provides a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.
Abstract: A genomic map of nearly 300,000 potential cis-regulatory sequences determined from diverse mouse tissues and cell types reveals active promoters, enhancers and CCCTC-binding factor sites encompassing 11% of the mouse genome and significantly expands annotation of mammalian regulatory sequences. The identification of cis-regulatory sequences in the mouse genome has lagged behind that of other model organisms. Here, a genomic map of nearly 300,000 potential cis-regulatory sequences has been experimentally determined from diverse mouse tissues and cell types. The map reveals active promoters, enhancers and CTCF (CCCTC-binding factor) sites in nearly 11% of the mouse genome and significantly expands the annotation of mammalian regulatory sequences. The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 × 109 bases of the mouse genome possess a high degree of conservation with the human genome1, so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. So far, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics has been a powerful tool for the discovery of these sequences2, but on its own it cannot resolve their temporal and spatial functions. Recently, ChIP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including humans, Drosophila melanogaster and Caenorhabditis elegans3,4,5. Here we apply the same experimental approach to a diverse set of 19 tissues and cell types in the mouse to produce a map of nearly 300,000 murine cis-regulatory sequences. The annotated sequences add up to 11% of the mouse genome, and include more than 70% of conserved non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we show that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.

1,350 citations

Journal ArticleDOI
14 Nov 2013-Nature
TL;DR: A comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C) is reported and suggests that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection of target genes by a ubiquitous transcription activator in a cell-specific manner.
Abstract: A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-α signalling in these cells. Unexpectedly, we found that TNF-α-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.

1,144 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
18 Dec 2014-Cell
TL;DR: In situ Hi-C is used to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types, identifying ∼10,000 loops that frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species.

5,945 citations

Journal ArticleDOI
17 May 2012-Nature
TL;DR: It is found that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
Abstract: The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories, and numerous models have been proposed for how chromosomes fold within chromosome territories. These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid advances in the study of three-dimensional genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide. Here we investigate the three-dimensional organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. Finally, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.

5,774 citations

Journal ArticleDOI
Anshul Kundaje1, Wouter Meuleman2, Wouter Meuleman1, Jason Ernst3, Misha Bilenky4, Angela Yen1, Angela Yen2, Alireza Heravi-Moussavi4, Pouya Kheradpour1, Pouya Kheradpour2, Zhizhuo Zhang2, Zhizhuo Zhang1, Jianrong Wang2, Jianrong Wang1, Michael J. Ziller2, Viren Amin5, John W. Whitaker, Matthew D. Schultz6, Lucas D. Ward1, Lucas D. Ward2, Abhishek Sarkar1, Abhishek Sarkar2, Gerald Quon1, Gerald Quon2, Richard Sandstrom7, Matthew L. Eaton2, Matthew L. Eaton1, Yi-Chieh Wu1, Yi-Chieh Wu2, Andreas R. Pfenning2, Andreas R. Pfenning1, Xinchen Wang1, Xinchen Wang2, Melina Claussnitzer1, Melina Claussnitzer2, Yaping Liu2, Yaping Liu1, Cristian Coarfa5, R. Alan Harris5, Noam Shoresh2, Charles B. Epstein2, Elizabeta Gjoneska2, Elizabeta Gjoneska1, Danny Leung8, Wei Xie8, R. David Hawkins8, Ryan Lister6, Chibo Hong9, Philippe Gascard9, Andrew J. Mungall4, Richard A. Moore4, Eric Chuah4, Angela Tam4, Theresa K. Canfield7, R. Scott Hansen7, Rajinder Kaul7, Peter J. Sabo7, Mukul S. Bansal2, Mukul S. Bansal1, Mukul S. Bansal10, Annaick Carles4, Jesse R. Dixon8, Kai How Farh2, Soheil Feizi2, Soheil Feizi1, Rosa Karlic11, Ah Ram Kim2, Ah Ram Kim1, Ashwinikumar Kulkarni12, Daofeng Li13, Rebecca F. Lowdon13, Ginell Elliott13, Tim R. Mercer14, Shane Neph7, Vitor Onuchic5, Paz Polak2, Paz Polak15, Nisha Rajagopal8, Pradipta R. Ray12, Richard C Sallari1, Richard C Sallari2, Kyle Siebenthall7, Nicholas A Sinnott-Armstrong2, Nicholas A Sinnott-Armstrong1, Michael Stevens13, Robert E. Thurman7, Jie Wu16, Bo Zhang13, Xin Zhou13, Arthur E. Beaudet5, Laurie A. Boyer1, Philip L. De Jager15, Philip L. De Jager2, Peggy J. Farnham17, Susan J. Fisher9, David Haussler18, Steven J.M. Jones19, Steven J.M. Jones4, Wei Li5, Marco A. Marra4, Michael T. McManus9, Shamil R. Sunyaev15, Shamil R. Sunyaev2, James A. Thomson20, Thea D. Tlsty9, Li-Huei Tsai2, Li-Huei Tsai1, Wei Wang, Robert A. Waterland5, Michael Q. Zhang21, Lisa Helbling Chadwick22, Bradley E. Bernstein2, Bradley E. Bernstein15, Bradley E. Bernstein6, Joseph F. Costello9, Joseph R. Ecker11, Martin Hirst4, Alexander Meissner2, Aleksandar Milosavljevic5, Bing Ren8, John A. Stamatoyannopoulos7, Ting Wang13, Manolis Kellis2, Manolis Kellis1 
19 Feb 2015-Nature
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

5,037 citations

Journal ArticleDOI
TL;DR: Canu, a successor of Celera Assembler that is specifically designed for noisy single-molecule sequences, is presented, demonstrating that Canu can reliably assemble complete microbial genomes and near-complete eukaryotic chromosomes using either Pacific Biosciences or Oxford Nanopore technologies.
Abstract: Long-read single-molecule sequencing has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. However, given the relatively high error rates of such technologies, efficient and accurate assembly of large repeats and closely related haplotypes remains challenging. We address these issues with Canu, a successor of Celera Assembler that is specifically designed for noisy single-molecule sequences. Canu introduces support for nanopore sequencing, halves depth-of-coverage requirements, and improves assembly continuity while simultaneously reducing runtime by an order of magnitude on large genomes versus Celera Assembler 8.2. These advances result from new overlapping and assembly algorithms, including an adaptive overlapping strategy based on tf-idf weighted MinHash and a sparse assembly graph construction that avoids collapsing diverged repeats and haplotypes. We demonstrate that Canu can reliably assemble complete microbial genomes and near-complete eukaryotic chromosomes using either Pacific Biosciences (PacBio) or Oxford Nanopore technologies and achieves a contig NG50 of >21 Mbp on both human and Drosophila melanogaster PacBio data sets. For assembly structures that cannot be linearly represented, Canu provides graph-based assembly outputs in graphical fragment assembly (GFA) format for analysis or integration with complementary phasing and scaffolding techniques. The combination of such highly resolved assembly graphs with long-range scaffolding information promises the complete and automated assembly of complex genomes.

4,806 citations