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https://www.readbyqxmd.com/read/28628007/direct-measurement-of-conformational-strain-energy-in-protofilaments-curling-outward-from-disassembling-microtubule-tips
#1
Jonathan W Driver, Elisabeth A Geyer, Megan E Bailey, Luke M Rice, Charles L Asbury
Disassembling microtubules can generate movement independently of motor enzymes, especially at kinetochores where they drive chromosome motility. A popular explanation is the 'conformational wave' model, in which protofilaments pull on the kinetochore as they curl outward from a disassembling tip. But whether protofilaments can work efficiently via this spring-like mechanism has been unclear. By modifying a previous assay to use recombinant tubulin and feedback-controlled laser trapping, we directly demonstrate the spring-like elasticity of curling protofilaments...
June 19, 2017: ELife
https://www.readbyqxmd.com/read/28623585/in-situ-hi-c-library-preparation-for-plants-to-study-their-three-dimensional-chromatin-interactions-on-a-genome-wide-scale
#2
Chang Liu
The spatial organization of the genome in the nucleus is critical for many cellular processes. It has been broadly accepted that the packing of chromatin inside the nucleus is not random, but structured at several hierarchical levels. The Hi-C method combines Chromatin Conformation Capture and high-throughput sequencing, which allows interrogating genome-wide chromatin interactions. Depending on the sequencing depth, chromatin packing patterns derived from Hi-C experiments can be viewed on a chromosomal scale or at a local genic level...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28615534/functional-dissection-of-breast-cancer-risk-associated-tert-promoter-variants
#3
Sonja Helbig, Leesa Wockner, Annick Bouendeu, Ursula Hille-Betz, Karen McCue, Juliet D French, Stacey L Edwards, Hilda A Pickett, Roger R Reddel, Georgia Chenevix-Trench, Thilo Dörk, Jonathan Beesley
The multi-cancer susceptibility locus at 5p15.33 includes TERT, encoding the telomerase catalytic subunit. Genome-wide association studies (GWAS) have identified six single nucleotide polymorphisms (SNPs) in the TERT promoter associated with decreased breast cancer risk, although the precise causal variants and their mechanisms of action have remained elusive. Luciferase reporter assays indicated that the protective haplotype reduced TERT promoter activity in human mammary epithelial and cancer cells in an estrogen-independent manner...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609784/genome-wide-profiling-of-s-mar-based-replicon-contact-sites
#4
Claudia Hagedorn, Andreas Gogol-Döring, Sabrina Schreiber, Jörg T Epplen, Hans J Lipps
Autonomously replicating vectors represent a simple and versatile model system for genetic modifications, but their localization in the nucleus and effect on endogenous gene expression is largely unknown. Using circular chromosome conformation capture we mapped genomic contact sites of S/MAR-based replicons in HeLa cells. The influence of cis-active sequences on genomic localization was assessed using replicons containing either an insulator sequence or an intron. While the original and the insulator-containing replicons displayed distinct contact sites, the intron-containing replicon showed a rather broad genomic contact pattern...
June 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28608466/crystal-structure-of-human-wbscr16-an-rcc1-like-protein-in-mitochondria
#5
Masako Koyama, Taeko Sasaki, Narie Sasaki, Yoshiyuki Matsuura
WBSCR16 (Williams-Beuren Syndrome Chromosomal Region 16) gene is located in a large deletion region of Williams-Beuren syndrome (WBS), which is a neurodevelopmental disorder. Although the relationship between WBSCR16 and WBS remains unclear, it has been reported that WBSCR16 is a member of a functional module that regulates mitochondrial 16S rRNA abundance and intra-mitochondrial translation. WBSCR16 has RCC1 (Regulator of Chromosome Condensation 1)-like amino acid sequence repeats but the function of WBSCR16 appears to be different from that of other RCC1 superfamily members...
June 12, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28604723/fish-ing-for-captured-contacts-towards-reconciling-fish-and-3c
#6
Geoffrey Fudenberg, Maxim Imakaev
Chromosome conformation capture (3C) and fluorescence in situ hybridization (FISH) are two widely used technologies that provide distinct readouts of 3D chromosome organization. While both technologies can assay locus-specific organization, how to integrate views from 3C, or genome-wide Hi-C, and FISH is far from solved. Contact frequency, measured by Hi-C, and spatial distance, measured by FISH, are often assumed to quantify the same phenomena and used interchangeably. Here, however, we demonstrate that contact frequency is distinct from average spatial distance, both in polymer simulations and in experimental data...
June 12, 2017: Nature Methods
https://www.readbyqxmd.com/read/28601046/lsd1-knockdown-reveals-novel-histone-lysine-methylation-in-human-breast-cancer-mcf-7-cells
#7
Yue Jin, Bo Huo, Xueqi Fu, Zhongyi Cheng, Jun Zhu, Yu Zhang, Tian Hao, Xin Hu
Histone lysine methylation, which plays an important role in the regulation of gene expression, genome stability, chromosome conformation and cell differentiation, is a dynamic process that is collaboratively regulated by lysine methyltransferases (KMTs) and lysine demethylases (KDMs). LSD1, the first identified KDMs, catalyzes the demethylation of mono- and di-methylated H3K4 and H3K9. Here, we systematically investigated the effects of LSD1 knockdown on histone methylations. Surprisingly, in addition to H3K4 and H3K9, the methylation level on other histone lysines, such as H3K27, H3K36 and H3K79, are also increased...
June 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28577753/cocaine-induced-chromatin-modifications-associate-with-increased-expression-and-three-dimensional-looping-of-auts2
#8
Olivia Engmann, Benoit Labonté, Amanda Mitchell, Pavel Bashtrykov, Erin S Calipari, Chaggai Rosenbluh, Yong-Hwee E Loh, Deena M Walker, Dominika Burek, Peter J Hamilton, Orna Issler, Rachael L Neve, Gustavo Turecki, Yasmin Hurd, Andrew Chess, Li Shen, Isabelle Mansuy, Albert Jeltsch, Schahram Akbarian, Eric J Nestler
BACKGROUND: Exposure to drugs of abuse alters the epigenetic landscape of the brain's reward regions, such as the nucleus accumbens. We investigated how combinations of chromatin modifications affect genes that regulate responses to cocaine. We focused on Auts2, a gene linked to human evolution and cognitive disorders, which displays strong clustering of cocaine-induced chromatin modifications in this brain region. METHODS: We combined chromosome conformation capture, circularized chromosome conformation capture, and related approaches with behavioral paradigms relevant to cocaine phenotypes...
May 5, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28566382/human-papillomavirus-major-capsid-protein-l1-remains-associated-with-the-incoming-viral-genome-throughout-the-entry-process
#9
Stephen DiGiuseppe, Malgorzata Bienkowska-Haba, Lucile G M Guion, Timothy R Keiffer, Martin Sapp
During infectious entry, acidification within the endosome triggers uncoating of the HPV capsid whereupon host cyclophilins facilitate the release of most of the major capsid protein, L1, from the minor capsid protein L2 and the viral genome. The L2/DNA complex traffics to the trans-Golgi network (TGN). Following the onset of mitosis, HPV-harboring transport vesicles bud from the TGN followed by association with mitotic chromosomes. During this time, the HPV genome remains in a vesicular compartment until the nucleus has completely reformed...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28549169/regulatory-dynamics-of-11p13-suggest-a-role-for-ehf-in-modifying-cf-lung-disease-severity
#10
Lindsay R Stolzenburg, Rui Yang, Jenny L Kerschner, Sara Fossum, Matthew Xu, Andrew Hoffmann, Kay-Marie Lamar, Sujana Ghosh, Sarah Wachtel, Shih-Hsing Leir, Ann Harris
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), but are not good predictors of lung phenotype. Genome-wide association studies (GWAS) previously identified additional genomic sites associated with CF lung disease severity. One of these, at chromosome 11p13, is an intergenic region between Ets homologous factor (EHF) and Apaf-1 interacting protein (APIP). Our goal was to determine the functional significance of this region, which being intergenic is probably regulatory...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28547585/aio-casilio-a-robust-crispr-cas9-pumilio-system-for-chromosome-labeling
#11
Shuxian Zhang, Zhan Song
The biological function of chromatin bases on its spatial organization and dynamic activities in different situations. Labeling and tracing of genomic sequences has been a huge challenge in studying the spatial dynamics of chromatin. We reported the development of 'all-in-one Casilio system (Aio-Casilio)', a new system that enables the labeling of endogenous genomic loci. The Aio-Casilio system consists of the dCas9 protein, mClover fused with the Pumilio and FBF proteins RNA-binding domain (PUF domain) and an U6-sgRNA appended with multiple PUF-binding site(s)...
May 25, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28544514/dynamic-enhancer-function-in-the-chromatin-context
#12
REVIEW
Ido Goldstein, Gordon L Hager
Enhancers serve as critical regulatory elements in higher eukaryotic cells. The characterization of enhancer function has evolved primarily from genome-wide methodologies, including chromatin immunoprecipitation (ChIP-seq), DNase-I hypersensitivity (DNase-seq), digital genomic footprinting (DGF), and the chromosome conformation capture techniques (3C, 4C, and Hi-C). These population-based assays average signals across millions of cells and lead to enhancer models characterized by static and sequential binding...
May 22, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28542722/a-homozygous-potentially-pathogenic-variant-in-the-paxbp1-gene-in-a-large-family-with-global-developmental-delay-and-myopathic-hypotonia
#13
Essa Alharby, Alia M Albalawi, Abdul Nasir, Sabri A Alhijji, Amer Mahmood, Khushnooda Ramzan, Firoz Abdusamad, Abdulkarim Aljohani, Osama Abdelsalam, Amr Eldardear, Sulman Basit
PAX binding protein 1 (PAXBP1) is an adaptor protein linking the transcription factor PAX3 and PAX7 to the histone methylation machinery. PAXBP1 is a nuclear protein and its high expression is known in brain cerebellar hemisphere and cerebellum. Moreover, it is also found in abundance in muscle precursor cells that are involved in myogenesis and skeletal muscles formation. Whole genome SNP genotyping and exome sequencing in a family with distinct syndrome of global developmental delay and hypotonia mapped the disease locus to the chromosome 21q22...
May 19, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28537556/the-dynamic-three-dimensional-organization-of-the-diploid-yeast-genome
#14
Seungsoo Kim, Ivan Liachko, Donna G Brickner, Kate Cook, William S Noble, Jason H Brickner, Jay Shendure, Maitreya J Dunham
The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. However, even in this well-studied model, it is unclear how homolog pairing in diploids or environmental conditions influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation using a polymer model, we observe significant homolog proximity that increases in saturated culture conditions...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28533516/asd-restricted-and-repetitive-behaviors-associated-at-17q21-33-genes-prioritized-by-expression-in-fetal-brains
#15
R M Cantor, L Navarro, H Won, R L Walker, J K Lowe, D H Geschwind
Autism spectrum disorder (ASD) is a behaviorally defined condition that manifests in infancy or early childhood as deficits in communication skills and social interactions. Often, restricted and repetitive behaviors (RRBs) accompany this disorder. ASD is polygenic and genetically complex, so we hypothesized that focusing analyses on intermediate core component phenotypes, such as RRBs, can reduce genetic heterogeneity and improve statistical power. Applying this approach, we mined Caucasian genome-wide association studies (GWAS) data from two of the largest ASD family cohorts, the Autism Genetics Resource Exchange and Autism Genome Project (AGP)...
May 23, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28532684/quantitative-determination-of-testosterone-levels-with-biolayer-interferometry
#16
Hao Zhang, Wei Li, Hong Luo, Guangming Xiong, Yuanhua Yu
Natural and synthetic steroid hormones are widely spread in the environment and are considered as pollutants due to their endocrine activities, even at low concentrations, which are harmful to human health. To detect steroid hormones in the environment, a novel biosensor system was developed based on the principle of biolayer interferometry. Detection is based on changes in the interference pattern of white light reflected from the surface of an optical fiber with bound biomolecules. Monitoring interactions between molecules does not require radioactive, enzymatic, or fluorescent labels...
May 19, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28526829/super-enhancers-and-broad-h3k4me3-domains-form-complex-gene-regulatory-circuits-involving-chromatin-interactions
#17
Fan Cao, Yiwen Fang, Hong Kee Tan, Yufen Goh, Jocelyn Yeen Hui Choy, Bryan Thean Howe Koh, Jiong Hao Tan, Nicolas Bertin, Aroul Ramadass, Ewan Hunter, Jayne Green, Matthew Salter, Alexandre Akoulitchev, Wilson Wang, Wee Joo Chng, Daniel G Tenen, Melissa J Fullwood
Stretched histone regions, such as super-enhancers and broad H3K4me3 domains, are associated with maintenance of cell identity and cancer. We connected super-enhancers and broad H3K4me3 domains in the K562 chronic myelogenous leukemia cell line as well as the MCF-7 breast cancer cell line with chromatin interactions. Super-enhancers and broad H3K4me3 domains showed higher association with chromatin interactions than their typical counterparts. Interestingly, we identified a subset of super-enhancers that overlap with broad H3K4me3 domains and show high association with cancer-associated genes including tumor suppressor genes...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512095/structure-based-mutations-in-the-herpes-simplex-virus-1-glycoprotein-b-ectodomain-arm-impart-a-slow-entry-phenotype
#18
Qing Fan, Sarah J Kopp, Sarah A Connolly, Richard Longnecker
Glycoprotein B (gB) is the conserved herpesvirus fusion protein, and it is required for the entry of herpesviruses. The structure of the postfusion conformation of gB has been solved for several herpesviruses; however, the gB prefusion crystal structure and the details of how the protein refolds from a prefusion to a postfusion form to mediate fusion have not been determined. Using structure-based mutagenesis, we previously reported that three mutations (I671A, H681A, and F683A) in the C-terminal arm of the gB ectodomain greatly reduced cell-cell fusion...
May 16, 2017: MBio
https://www.readbyqxmd.com/read/28511927/coordinated-regulation-of-ifitm1-2-and-3-genes-by-an-ifn-responsive-enhancer-through-long-range-chromatin-interactions
#19
Ping Li, Ming-Lei Shi, Wen-Long Shen, Zhang Zhang, De-Jian Xie, Xiang-Yuan Zhang, Chao He, Yan Zhang, Zhi-Hu Zhao
Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 are a family of interferon (IFN)-induced transmembrane proteins that block entry of a broad spectrum of pathogens. However, the transcriptional regulation of these genes, especially whether there exists any enhancers and their roles during the IFN induction process remain elusive. Here, combining episomal luciferase reporter assay and in vivo genome editing, we identified an IFNβ-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFNβ-induced expression of IFITM1, 2 and 3 genes, thus contributing to IFNβ-mediated resistance to influenza A virus (IAV) infection...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28510289/genome-organization-during-the-cell-cycle-unity-in-division
#20
REVIEW
Rosela Golloshi, Jacob T Sanders, Rachel Patton McCord
During the cell cycle, the genome must undergo dramatic changes in structure, from a decondensed, yet highly organized interphase structure to a condensed, generic mitotic chromosome and then back again. For faithful cell division, the genome must be replicated and chromosomes and sister chromatids physically segregated from one another. Throughout these processes, there is feedback and tension between the information-storing role and the physical properties of chromosomes. With a combination of recent techniques in fluorescence microscopy, chromosome conformation capture (Hi-C), biophysical experiments, and computational modeling, we can now attribute mechanisms to many long-observed features of chromosome structure changes during cell division...
May 16, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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