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16 papers 100 to 500 followers Papers considered for a senior undergraduate seminar in epicene tics.
Gungor Ozer, Antoni Luque, Tamar Schlick
The structure of chromatin, affected by many factors from DNA linker lengths to posttranslational modifications, is crucial to the regulation of eukaryotic cells. Combined experimental and computational methods have led to new insights into its structural and dynamical features, from interactions due to the flexible core histone tails or linker histones to the physical mechanism driving the formation of chromosomal domains. Here we present a perspective of recent advances in chromatin modeling techniques at the atomic, mesoscopic, and chromosomal scales with a view toward developing multiscale computational strategies to integrate such findings...
April 2015: Current Opinion in Structural Biology
Alexander M Tsankov, Hongcang Gu, Veronika Akopian, Michael J Ziller, Julie Donaghey, Ido Amit, Andreas Gnirke, Alexander Meissner
Pluripotent stem cells provide a powerful system to dissect the underlying molecular dynamics that regulate cell fate changes during mammalian development. Here we report the integrative analysis of genome-wide binding data for 38 transcription factors with extensive epigenome and transcriptional data across the differentiation of human embryonic stem cells to the three germ layers. We describe core regulatory dynamics and show the lineage-specific behaviour of selected factors. In addition to the orchestrated remodelling of the chromatin landscape, we find that the binding of several transcription factors is strongly associated with specific loss of DNA methylation in one germ layer, and in many cases a reciprocal gain in the other layers...
February 19, 2015: Nature
Anshul Kundaje, Wouter Meuleman, Jason Ernst, Misha Bilenky, Angela Yen, Alireza Heravi-Moussavi, Pouya Kheradpour, Zhizhuo Zhang, Jianrong Wang, Michael J Ziller, Viren Amin, John W Whitaker, Matthew D Schultz, Lucas D Ward, Abhishek Sarkar, Gerald Quon, Richard S Sandstrom, Matthew L Eaton, Yi-Chieh Wu, Andreas R Pfenning, Xinchen Wang, Melina Claussnitzer, Yaping Liu, Cristian Coarfa, R Alan Harris, Noam Shoresh, Charles B Epstein, Elizabeta Gjoneska, Danny Leung, Wei Xie, R David Hawkins, Ryan Lister, Chibo Hong, Philippe Gascard, Andrew J Mungall, Richard Moore, Eric Chuah, Angela Tam, Theresa K Canfield, R Scott Hansen, Rajinder Kaul, Peter J Sabo, Mukul S Bansal, Annaick Carles, Jesse R Dixon, Kai-How Farh, Soheil Feizi, Rosa Karlic, Ah-Ram Kim, Ashwinikumar Kulkarni, Daofeng Li, Rebecca Lowdon, GiNell Elliott, Tim R Mercer, Shane J Neph, Vitor Onuchic, Paz Polak, Nisha Rajagopal, Pradipta Ray, Richard C Sallari, Kyle T Siebenthall, Nicholas A Sinnott-Armstrong, Michael Stevens, Robert E Thurman, Jie Wu, Bo Zhang, Xin Zhou, Arthur E Beaudet, Laurie A Boyer, Philip L De Jager, Peggy J Farnham, Susan J Fisher, David Haussler, Steven J M Jones, Wei Li, Marco A Marra, Michael T McManus, Shamil Sunyaev, James A Thomson, Thea D Tlsty, Li-Huei Tsai, Wei Wang, Robert A Waterland, Michael Q Zhang, Lisa H Chadwick, Bradley E Bernstein, Joseph F Costello, Joseph R Ecker, Martin Hirst, Alexander Meissner, Aleksandar Milosavljevic, Bing Ren, John A Stamatoyannopoulos, Ting Wang, Manolis Kellis
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...
February 19, 2015: Nature
Jesse R Dixon, Inkyung Jung, Siddarth Selvaraj, Yin Shen, Jessica E Antosiewicz-Bourget, Ah Young Lee, Zhen Ye, Audrey Kim, Nisha Rajagopal, Wei Xie, Yarui Diao, Jing Liang, Huimin Zhao, Victor V Lobanenkov, Joseph R Ecker, James A Thomson, Bing Ren
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...
February 19, 2015: Nature
Nian Liu, Qing Dai, Guanqun Zheng, Chuan He, Marc Parisien, Tao Pan
RNA-binding proteins control many aspects of cellular biology through binding single-stranded RNA binding motifs (RBMs). However, RBMs can be buried within their local RNA structures, thus inhibiting RNA-protein interactions. N(6)-methyladenosine (m(6)A), the most abundant and dynamic internal modification in eukaryotic messenger RNA, can be selectively recognized by the YTHDF2 protein to affect the stability of cytoplasmic mRNAs, but how m(6)A achieves its wide-ranging physiological role needs further exploration...
February 26, 2015: Nature
Liming Liang, Saffron A G Willis-Owen, Catherine Laprise, Kenny C C Wong, Gwyneth A Davies, Thomas J Hudson, Aristea Binia, Julian M Hopkin, Ivana V Yang, Elin Grundberg, Stephan Busche, Marie Hudson, Lars Rönnblom, Tomi M Pastinen, David A Schwartz, G Mark Lathrop, Miriam F Moffatt, William O C M Cookson
Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever and allergic asthma. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population...
April 30, 2015: Nature
Elizabeta Gjoneska, Andreas R Pfenning, Hansruedi Mathys, Gerald Quon, Anshul Kundaje, Li-Huei Tsai, Manolis Kellis
Alzheimer's disease (AD) is a severe age-related neurodegenerative disorder characterized by accumulation of amyloid-β plaques and neurofibrillary tangles, synaptic and neuronal loss, and cognitive decline. Several genes have been implicated in AD, but chromatin state alterations during neurodegeneration remain uncharacterized. Here we profile transcriptional and chromatin state dynamics across early and late pathology in the hippocampus of an inducible mouse model of AD-like neurodegeneration. We find a coordinated downregulation of synaptic plasticity genes and regulatory regions, and upregulation of immune response genes and regulatory regions, which are targeted by factors that belong to the ETS family of transcriptional regulators, including PU...
February 19, 2015: Nature
Danny Leung, Inkyung Jung, Nisha Rajagopal, Anthony Schmitt, Siddarth Selvaraj, Ah Young Lee, Chia-An Yen, Shin Lin, Yiing Lin, Yunjiang Qiu, Wei Xie, Feng Yue, Manoj Hariharan, Pradipta Ray, Samantha Kuan, Lee Edsall, Hongbo Yang, Neil C Chi, Michael Q Zhang, Joseph R Ecker, Bing Ren
Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here we delineate allelic chromatin modifications and transcriptomes among a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy. The resulting large collection of haplotype-resolved epigenomic maps reveals extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences...
February 19, 2015: Nature
Casey E Romanoski, Christopher K Glass, Hendrik G Stunnenberg, Laurence Wilson, Genevieve Almouzni
No abstract text is available yet for this article.
February 19, 2015: Nature
Magdalena Skipper, Alex Eccleston, Noah Gray, Therese Heemels, Nathalie Le Bot, Barbara Marte, Ursula Weiss
No abstract text is available yet for this article.
February 19, 2015: Nature
(no author information available yet)
No abstract text is available yet for this article.
February 19, 2015: Nature
Umeharu Ohto, Takuma Shibata, Hiromi Tanji, Hanako Ishida, Elena Krayukhina, Susumu Uchiyama, Kensuke Miyake, Toshiyuki Shimizu
Innate immunity serves as the first line of defence against invading pathogens such as bacteria and viruses. Toll-like receptors (TLRs) are examples of innate immune receptors, which sense specific molecular patterns from pathogens and activate immune responses. TLR9 recognizes bacterial and viral DNA containing the cytosine-phosphate-guanine (CpG) dideoxynucleotide motif. The molecular basis by which CpG-containing DNA (CpG-DNA) elicits immunostimulatory activity via TLR9 remains to be elucidated. Here we show the crystal structures of three forms of TLR9: unliganded, bound to agonistic CpG-DNA, and bound to inhibitory DNA (iDNA)...
April 30, 2015: Nature
Verena K Maier, Caitlin M Feeney, Jordan E Taylor, Amanda L Creech, Jana W Qiao, Attila Szanto, Partha P Das, Nicholas Chevrier, Catherine Cifuentes-Rojas, Stuart H Orkin, Steven A Carr, Jacob D Jaffe, Philipp Mertins, Jeannie T Lee
Cell-type specific gene silencing by histone H3 lysine 27 and lysine 9 methyltransferase complexes PRC2 and G9A-GLP is crucial both during development and to maintain cell identity. Although studying their interaction partners has yielded valuable insight into their functions, how these factors are regulated on a network level remains incompletely understood. Here, we present a new approach that combines quantitative interaction proteomics with global chromatin profiling to functionally characterize repressive chromatin modifying protein complexes in embryonic stem cells...
June 2015: Molecular & Cellular Proteomics: MCP
Julien Pompon, Mariano A Garcia-Blanco
Noncoding RNAs have regulatory capabilities that evolution harnesses to fulfill diverse functions. Lee et al. show that a noncoding RNA from Epstein-Barr virus recruits a host transcription factor to silence virus gene expression and propose that it does this through base-pairing with nascent viral transcripts.
February 12, 2015: Cell
Olof Leimar, John M McNamara
An organism's phenotype can be influenced by maternal cues and directly perceived environmental cues, as well as by its genotype at polymorphic loci, which can be interpreted as a genetic cue. In fluctuating environments, natural selection favors organisms that efficiently integrate different sources of information about the likely success of phenotypic alternatives. In such situations, it can be beneficial to pass on maternal cues that offspring can respond to. A maternal cue could be based on environmental cues directly perceived by the mother but also partly on cues that were passed on by the grandmother...
March 2015: American Naturalist
Leigh C Latta, Mica Peacock, David J Civitello, Jeffry L Dudycha, Jesse M Meik, Sarah Schaack
Understanding the context dependence of mutation represents the current frontier of mutation research. In particular, understanding how traits vary in their abilities to accrue mutational variation and how the environment influences expression of mutant phenotypes yields insight into evolutionary processes. We conducted phenotypic assays in four environments using a set of Daphnia pulex mutation accumulation lines to examine the context dependence of mutation. Life-history traits accrued mutational variance faster than morphological traits when considered in individual environments...
February 2015: American Naturalist
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