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https://www.readbyqxmd.com/read/28938092/ctcf-mediated-enhancer-promoter-interaction-is-a-critical-regulator-of-cell-to-cell-variation-of-gene-expression
#1
Gang Ren, Wenfei Jin, Kairong Cui, Joseph Rodrigez, Gangqing Hu, Zhiying Zhang, Daniel R Larson, Keji Zhao
Recent studies indicate that even a homogeneous population of cells display heterogeneity in gene expression and response to environmental stimuli. Although promoter structure critically influences the cell-to-cell variation of gene expression in bacteria and lower eukaryotes, it remains unclear what controls the gene expression noise in mammals. Here we report that CTCF decreases cell-to-cell variation of expression by stabilizing enhancer-promoter interaction. We show that CTCF binding sites are interwoven with enhancers within topologically associated domains (TADs) and a positive correlation is found between CTCF binding and the activity of the associated enhancers...
September 21, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28936982/optimization-and-quality-control-of-genome-wide-hi-c-library-preparation
#2
Xiang-Yuan Zhang, Chao He, Bing-Yu Ye, De-Jian Xie, Ming-Lei Shi, Yan Zhang, Wen-Long Shen, Ping Li, Zhi-Hu Zhao
Highest-throughput chromosome conformation capture (Hi-C) is one of the key assays for genome- wide chromatin interaction studies. It is a time-consuming process that involves many steps and many different kinds of reagents, consumables, and equipments. At present, the reproducibility is unsatisfactory. By optimizing the key steps of the Hi-C experiment, such as crosslinking, pretreatment of digestion, inactivation of restriction enzyme, and in situ ligation etc., we established a robust Hi-C procedure and prepared two biological replicates of Hi-C libraries from the GM12878 cells...
September 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28913417/parasite-biodiversity-faces-extinction-and-redistribution-in-a-changing-climate
#3
Colin J Carlson, Kevin R Burgio, Eric R Dougherty, Anna J Phillips, Veronica M Bueno, Christopher F Clements, Giovanni Castaldo, Tad A Dallas, Carrie A Cizauskas, Graeme S Cumming, Jorge Doña, Nyeema C Harris, Roger Jovani, Sergey Mironov, Oliver C Muellerklein, Heather C Proctor, Wayne M Getz
Climate change is a well-documented driver of both wildlife extinction and disease emergence, but the negative impacts of climate change on parasite diversity are undocumented. We compiled the most comprehensive spatially explicit data set available for parasites, projected range shifts in a changing climate, and estimated extinction rates for eight major parasite clades. On the basis of 53,133 occurrences capturing the geographic ranges of 457 parasite species, conservative model projections suggest that 5 to 10% of these species are committed to extinction by 2070 from climate-driven habitat loss alone...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28910577/subnuclear-distribution-of-proteins-links-with-genome-architecture
#4
Fouziya R Shah, Younus A Bhat, Ajazul H Wani
Metazoan genomes have a hierarchal 3-dimensional (3D) organization scaling from nucleosomes, loops, topologically associating domains (TADs), compartments, to chromosome territories. The 3D organization of genome has been linked with development, differentiation and disease. However, the principles governing the 3D chromatin architecture are just beginning to get unraveled. The nucleus has very high concentration of proteins and these proteins are either diffusely distributed throughout the nucleus, or aggregated in the form of foci/bodies/clusters/speckles or in combination of both...
September 14, 2017: Nucleus
https://www.readbyqxmd.com/read/28902867/analysis-of-the-relationship-between-coexpression-domains-and-chromatin-3d-organization
#5
María E Soler-Oliva, Jose A Guerrero-Martínez, Valentina Bachetti, Jose C Reyes
Gene order is not random in eukaryotic chromosomes, and co-regulated genes tend to be clustered. The mechanisms that determine co-regulation of large regions of the genome and its connection with chromatin three-dimensional (3D) organization are still unclear however. Here we have adapted a recently described method for identifying chromatin topologically associating domains (TADs) to identify coexpression domains (which we term "CODs"). Using human normal breast and breast cancer RNA-seq data, we have identified approximately 500 CODs...
September 13, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28890950/creating-conditions-for-patients-values-to-emerge-in-clinical-conversations-perspectives-of-health-care-team-members
#6
Andrew B L Berry, Catherine Lim, Andrea L Hartzler, Tad Hirsch, Evette Ludman, Edward H Wagner, James D Ralston
Eliciting, understanding, and honoring patients' values- the things most important to them in daily life-is a cornerstone of patient-centered care. However, this rarely occurs explicitly as a routine part of clinical practice. This is particularly problematic for individuals with multiple chronic conditions (MCC) because they face difficult choices about how to balance competing demands for self-care in accordance with their values. In this study, we sought to inform the design of interventions to support conversations about patient values between patients with MCC and their health care providers...
June 2017: DIS (Des Interact Syst Conf)
https://www.readbyqxmd.com/read/28890949/designing-contestability-interaction-design-machine-learning-and-mental-health
#7
Tad Hirsch, Kritzia Merced, Shrikanth Narayanan, Zac E Imel, David C Atkins
We describe the design of an automated assessment and training tool for psychotherapists to illustrate challenges with creating interactive machine learning (ML) systems, particularly in contexts where human life, livelihood, and wellbeing are at stake. We explore how existing theories of interaction design and machine learning apply to the psychotherapy context, and identify "contestability" as a new principle for designing systems that evaluate human behavior. Finally, we offer several strategies for making ML systems more accountable to human actors...
June 2017: Drosophila Information Service
https://www.readbyqxmd.com/read/28881104/bioactive-macrocyclic-inhibitors-of-the-pd-1-pd-l1-immune-checkpoint
#8
Katarzyna Magiera-Mularz, Lukasz Skalniak, Krzysztof M Zak, Bogdan Musielak, Ewa Rudzinska-Szostak, Łukasz Berlicki, Justyna Kocik, Przemyslaw Grudnik, Dominik Sala, Tryfonas Zizigas-Zarganis, Shabnam Shaabani, Alexander Dömling, Grzegorz Dubin, Tad A Holak
Blockade of the immunoinhibitory PD-1/PD-L1 pathway using monoclonal antibodies has shown impressive results with durable clinical antitumor responses. Anti-PD-1 and anti-PD-L1 antibodies have now been approved for the treatment of a number of tumor types whereas the development of small molecules targeting immune checkpoints lags far behind. Here we characterize two classes of macrocyclic-peptide inhibitors directed at the PD-1/PD-L1 pathway. We show that these macrocyclics act by directly binding to PD-L1 and that they are capable of antagonizing PD-L1 signaling and, similarly to antibodies, can restore the function of T-cells...
September 7, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28874668/topologically-associating-domains-are-ancient-features-that-coincide-with-metazoan-clusters-of-extreme-noncoding-conservation
#9
Nathan Harmston, Elizabeth Ing-Simmons, Ge Tan, Malcolm Perry, Matthias Merkenschlager, Boris Lenhard
Developmental genes in metazoan genomes are surrounded by dense clusters of conserved noncoding elements (CNEs). CNEs exhibit unexplained extreme levels of sequence conservation, with many acting as developmental long-range enhancers. Clusters of CNEs define the span of regulatory inputs for many important developmental regulators and have been described previously as genomic regulatory blocks (GRBs). Their function and distribution around important regulatory genes raises the question of how they relate to 3D conformation of these loci...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28867287/dynamic-control-of-x-chromosome-conformation-and-repression-by-a-histone-h4k20-demethylase
#10
Katjuša Brejc, Qian Bian, Satoru Uzawa, Bayly S Wheeler, Erika C Anderson, David S King, Philip J Kranzusch, Christine G Preston, Barbara J Meyer
Chromatin modification and higher-order chromosome structure play key roles in gene regulation, but their functional interplay in controlling gene expression is elusive. We have discovered the machinery and mechanism underlying the dynamic enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during C. elegans dosage compensation and demonstrated H4K20me1's pivotal role in regulating higher-order chromosome structure and X-chromosome-wide gene expression. The structure and the activity of the dosage compensation complex (DCC) subunit DPY-21 define a Jumonji demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28863138/5c-analysis-of-the-epidermal-differentiation-complex-locus-reveals-distinct-chromatin-interaction-networks-between-gene-rich-and-gene-poor-tads-in-skin-epithelial-cells
#11
Krzysztof Poterlowicz, Joanne L Yarker, Igor Malashchuk, Brian R Lajoie, Andrei N Mardaryev, Michal R Gdula, Andrey A Sharov, Terumi Kohwi-Shigematsu, Vladimir A Botchkarev, Michael Y Fessing
Mammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28861108/gene-functioning-and-storage-within-a-folded-genome
#12
REVIEW
Sergey V Razin, Sergey V Ulianov
In mammals, genomic DNA that is roughly 2 m long is folded to fit the size of the cell nucleus that has a diameter of about 10 μm. The folding of genomic DNA is mediated via assembly of DNA-protein complex, chromatin. In addition to the reduction of genomic DNA linear dimensions, the assembly of chromatin allows to discriminate and to mark active (transcribed) and repressed (non-transcribed) genes. Consequently, epigenetic regulation of gene expression occurs at the level of DNA packaging in chromatin. Taking into account the increasing attention of scientific community toward epigenetic systems of gene regulation, it is very important to understand how DNA folding in chromatin is related to gene activity...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28855365/estimating-parasite-host-range
#13
Tad Dallas, Shan Huang, Charles Nunn, Andrew W Park, John M Drake
Estimating the number of host species that a parasite can infect (i.e. host range) provides key insights into the evolution of host specialism and is a central concept in disease ecology. Host range is rarely estimated in real systems, however, because variation in species relative abundance and the detection of rare species makes it challenging to confidently estimate host range. We applied a non-parametric richness indicator to estimate host range in simulated and empirical data, allowing us to assess the influence of sampling heterogeneity and data completeness...
August 30, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28852764/erratum-to-ablation-of-cyclase-associated-protein-2-cap2-leads-to-cardiomyopathy
#14
Vivek S Peche, Tad A Holak, Bhagyashri D Burgute, Kosmas Kosmas, Sushant P Kale, F Thomas Wunderlich, Fatiha Elhamine, Robert Stehle, Gabriele Pfitzer, Klaus Nohroudi, Klaus Addicks, Florian Stöckigt, Jan W Schrickel, Julia Gallinger, Michael Schleicher, Angelika A Noegel
No abstract text is available yet for this article.
August 29, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28834715/bridging-microscopic-and-macroscopic-mechanisms-of-p53-mdm2-binding-with-kinetic-network-models
#15
Guangfeng Zhou, George A Pantelopulos, Sudipto Mukherjee, Vincent A Voelz
Under normal cellular conditions, the tumor suppressor protein p53 is kept at low levels in part due to ubiquitination by MDM2, a process initiated by binding of MDM2 to the intrinsically disordered transactivation domain (TAD) of p53. Many experimental and simulation studies suggest that disordered domains such as p53 TAD bind their targets nonspecifically before folding to a tightly associated conformation, but the microscopic details are unclear. Toward a detailed prediction of binding mechanisms, pathways, and rates, we have performed large-scale unbiased all-atom simulations of p53-MDM2 binding...
August 22, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28831003/vertebrate-like-cryptochrome-2-from-monarch-regulates-circadian-transcription-via-independent-repression-of-clock-and-bmal1-activity
#16
Ying Zhang, Matthew J Markert, Shayna C Groves, Paul E Hardin, Christine Merlin
Circadian repression of CLOCK-BMAL1 by PERIOD and CRYPTOCHROME (CRY) in mammals lies at the core of the circadian timekeeping mechanism. CRY repression of CLOCK-BMAL1 and regulation of circadian period are proposed to rely primarily on competition for binding with coactivators on an α-helix located within the transactivation domain (TAD) of the BMAL1 C terminus. This model has, however, not been tested in vivo. Here, we applied CRISPR/Cas9-mediated mutagenesis in the monarch butterfly (Danaus plexippus), which possesses a vertebrate-like CRY (dpCRY2) and an ortholog of BMAL1, to show that insect CRY2 regulates circadian repression through TAD α-helix-dependent and -independent mechanisms...
August 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28827502/risk-factors-associated-with-cephalomedullary-nail-cutout-in-the-treatment-of-trochanteric-hip-fractures
#17
David J Ciufo, Douglas A Zaruta, Jason S Lipof, Kyle T Judd, John T Gorczyca, John P Ketz
OBJECTIVES: To evaluate the association of cephalomedullary nail cutout in trochanteric femur fractures with the presence of the following radiographic variables: lateral wall fracture, posteromedial fragment, angular malreduction, residual basicervical fracture gapping, screw placement, and tip-apex distance (TAD). DESIGN: Retrospective review. SETTING: Academic medical center. PATIENTS: A total of 362 patients were included in the study...
August 12, 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28826674/evolutionarily-conserved-principles-predict-3d-chromatin-organization
#18
M Jordan Rowley, Michael H Nichols, Xiaowen Lyu, Masami Ando-Kuri, I Sarahi M Rivera, Karen Hermetz, Ping Wang, Yijun Ruan, Victor G Corces
Topologically associating domains (TADs), CTCF loop domains, and A/B compartments have been identified as important structural and functional components of 3D chromatin organization, yet the relationship between these features is not well understood. Using high-resolution Hi-C and HiChIP, we show that Drosophila chromatin is organized into domains we term compartmental domains that correspond precisely with A/B compartments at high resolution. We find that transcriptional state is a major predictor of Hi-C contact maps in several eukaryotes tested, including C...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28821190/fibromatosis-of-the-breast-diagnostic-accuracy-of-core-needle-biopsy
#19
M Gabriela Kuba, Susan C Lester, Catherine S Giess, Monica M Bertagnolli, Tad J Wieczorek, Jane E Brock
Objectives: Fibromatosis of the breast is an uncommon neoplasm with potential for local recurrence. Treatment has traditionally been surgical excision with current trends toward conservative management. Given the option of observation after diagnosis by core needle biopsy (CNB), we sought to evaluate the accuracy of CNB for diagnosing fibromatosis. Methods: We identified a total of 31 cases in which fibromatosis had been diagnosed or included in the differential diagnosis on a CNB, an excision, or both...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28807920/mediator-tail-module-is-required-for-tac1-activated-cdr1-expression-and-azole-resistance-in-candida-albicans
#20
Zhongle Liu, Lawrence C Myers
The human fungal pathogen Candida albicans develops drug resistance after long-term exposure to azole drugs in the treatment of chronic candidiasis. Gain-of-function (GOF) mutations in the transcription factor Tac1, and the consequent expression of its targets, drug efflux pumps Cdr1 and Cdr2, are a common mechanism by which C. albicans acquires fluconazole resistance. The mechanism by which GOF mutations hyperactivate Tac1 is currently unknown. Here, we define a transcriptional activation domain (TAD) at the C-terminus of Tac1...
August 14, 2017: Antimicrobial Agents and Chemotherapy
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