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https://www.readbyqxmd.com/read/27911788/near-atomic-structural-model-for-bacterial-dna-replication-initiation-complex-and-its-functional-insights
#1
Masahiro Shimizu, Yasunori Noguchi, Yukari Sakiyama, Hironori Kawakami, Tsutomu Katayama, Shoji Takada
Upon DNA replication initiation in Escherichia coli, the initiator protein DnaA forms higher-order complexes with the chromosomal origin oriC and a DNA-bending protein IHF. Although tertiary structures of DnaA and IHF have previously been elucidated, dynamic structures of oriC-DnaA-IHF complexes remain unknown. Here, combining computer simulations with biochemical assays, we obtained models at almost-atomic resolution for the central part of the oriC-DnaA-IHF complex. This complex can be divided into three subcomplexes; the left and right subcomplexes include pentameric DnaA bound in a head-to-tail manner and the middle subcomplex contains only a single DnaA...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27903283/systematic-analysis-of-chromatin-interactions-at-disease-associated-loci-links-novel-candidate-genes-to-inflammatory-bowel-disease
#2
Claartje A Meddens, Magdalena Harakalova, Noortje A M van den Dungen, Hassan Foroughi Asl, Hemme J Hijma, Edwin P J G Cuppen, Johan L M Björkegren, Folkert W Asselbergs, Edward E S Nieuwenhuis, Michal Mokry
BACKGROUND: Genome-wide association studies (GWAS) have revealed many susceptibility loci for complex genetic diseases. For most loci, the causal genes have not been identified. Currently, the identification of candidate genes is predominantly based on genes that localize close to or within identified loci. We have recently shown that 92 of the 163 inflammatory bowel disease (IBD)-loci co-localize with non-coding DNA regulatory elements (DREs). Mutations in DREs can contribute to IBD pathogenesis through dysregulation of gene expression...
November 30, 2016: Genome Biology
https://www.readbyqxmd.com/read/27899641/3d-genome-structure-modeling-by-lorentzian-objective-function
#3
Tuan Trieu, Jianlin Cheng
The 3D structure of the genome plays a vital role in biological processes such as gene interaction, gene regulation, DNA replication and genome methylation. Advanced chromosomal conformation capture techniques, such as Hi-C and tethered conformation capture, can generate chromosomal contact data that can be used to computationally reconstruct 3D structures of the genome. We developed a novel restraint-based method that is capable of reconstructing 3D genome structures utilizing both intra-and inter-chromosomal contact data...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27894997/structural-and-evolutionary-analyses-reveal-determinants-of-dna-binding-specificities-of-nucleoid-associated-proteins-hu-and-ihf
#4
Debayan Dey, Valakunja Nagaraja, Suryanarayanarao Ramakumar
Nucleoid-associated proteins (NAPs) are chromosome-organizing factors, which affect the transcriptional landscape of a bacterial cell. HU is an NAP, which binds to DNA with a broad specificity while homologous IHF (Integration Host Factor), binds DNA with moderately higher specificity. Specificity and differential binding affinity of HU/IHF proteins towards their target binding sites play a crucial role in their regulatory dynamics. Decades of biochemical and genomic studies have been carried out for HU and IHF like proteins...
November 25, 2016: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/27869158/mapping-the-3d-genome-aiming-for-consilience
#5
Job Dekker
The spatial organization of genomes is studied using microscopy- and chromosome conformation capture (3C)-based methods. The two types of methods produce data that are often consistent, but there are cases where they appear discordant. These cases provide opportunities to derive better models of chromatin folding, which can reconcile the datasets.
November 21, 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27866097/current-therapy-and-the-evolving-molecular-landscape-of-paediatric-ependymoma
#6
REVIEW
Soumen Khatua, Vijay Ramaswamy, Eric Bouffet
Ependymomas are the third commonest paediatric central nervous system (CNS) tumour, accounting for 6-12% of brain tumours in children. The management of these tumours has seen considerable changes over the last two decades, leading to a significant improvement in outcomes. However, despite advances in neurosurgical, neuroimaging and postoperative adjuvant therapy, management of these tumours remain challenging, and recurrence occurs in over 50% of cases, particularly when complete resection is not achieved prior to conformal radiotherapy...
November 17, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27863237/the-ties-that-bind-mapping-the-dynamic-enhancer-promoter-interactome
#7
REVIEW
Cailyn H Spurrell, Diane E Dickel, Axel Visel
Coupling chromosome conformation capture to molecular enrichment for promoter-containing DNA fragments enables the systematic mapping of interactions between individual distal regulatory sequences and their target genes. In this Minireview, we describe recent progress in the application of this technique and related complementary approaches to gain insight into the lineage- and cell-type-specific dynamics of interactions between regulators and gene promoters.
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27856763/normal-chromosome-conformation-depends-on-subtelomeric-facultative-heterochromatin-in-neurospora-crassa
#8
Andrew D Klocko, Tereza Ormsby, Jonathan M Galazka, Neena A Leggett, Miki Uesaka, Shinji Honda, Michael Freitag, Eric U Selker
High-throughput chromosome conformation capture (Hi-C) analyses revealed that the 3D structure of the Neurospora crassa genome is dominated by intra- and interchromosomal links between regions of heterochromatin, especially constitutive heterochromatin. Elimination of trimethylation of lysine 9 on histone H3 (H3K9me3) or its binding partner Heterochromatin Protein 1 (HP1)-both prominent features of constitutive heterochromatin-have little effect on the Hi-C pattern. It remained possible that di- or trimethylation of lysine 27 on histone H3 (H3K27me2/3), which becomes localized in regions of constitutive heterochromatin when H3K9me3 or HP1 are lost, plays a critical role in the 3D structure of the genome...
November 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27851967/a-compendium-of-chromatin-contact-maps-reveals-spatially-active-regions-in-the-human-genome
#9
Anthony D Schmitt, Ming Hu, Inkyung Jung, Zheng Xu, Yunjiang Qiu, Catherine L Tan, Yun Li, Shin Lin, Yiing Lin, Cathy L Barr, Bing Ren
The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, but genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we find topologically associating domains highly conserved in different tissues...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27846223/combgap-promotes-ovarian-niche-development-and-chromatin-association-of-ecr-binding-regions-in-br-c
#10
Anna Hitrik, Malka Popliker, Dana Gancz, Zohar Mukamel, Aviezer Lifshitz, Omer Schwartzman, Amos Tanay, Lilach Gilboa
The development of niches for tissue-specific stem cells is an important aspect of stem cell biology. Determination of niche size and niche numbers during organogenesis involves precise control of gene expression. How this is achieved in the context of a complex chromatin landscape is largely unknown. Here we show that the nuclear protein Combgap (Cg) supports correct ovarian niche formation in Drosophila by controlling ecdysone-Receptor (EcR)- mediated transcription and long-range chromatin contacts in the broad locus (BR-C)...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27843713/deconvoluting-simulated-metagenomes-the-performance-of-hard-and-soft-clustering-algorithms-applied-to-metagenomic-chromosome-conformation-capture-3c
#11
Matthew Z DeMaere, Aaron E Darling
BACKGROUND: Chromosome conformation capture, coupled with high throughput DNA sequencing in protocols like Hi-C and 3C-seq, has been proposed as a viable means of generating data to resolve the genomes of microorganisms living in naturally occuring environments. Metagenomic Hi-C and 3C-seq datasets have begun to emerge, but the feasibility of resolving genomes when closely related organisms (strain-level diversity) are present in the sample has not yet been systematically characterised...
2016: PeerJ
https://www.readbyqxmd.com/read/27832542/unbiased-interrogation-of-3d-genome-topology-using-chromosome-conformation-capture-coupled-to-high-throughput-sequencing-4c-seq
#12
Rutger W W Brouwer, Mirjam C G N van den Hout, Wilfred F J van IJcken, Eric Soler, Ralph Stadhouders
The development and widespread implementation of chromosome conformation capture (3C) technology has allowed unprecedented new insight into how chromosomes are folded in three-dimensional (3D) space. 3C and its derivatives have contributed tremendously to the now widely accepted view that genome topology plays an important role in many major cellular processes, at a chromosome-wide scale, but certainly also at the level of individual genetic loci. A particularly popular application of 3C technology is to study transcriptional regulation, allowing researchers to draw maps of gene regulatory connections beyond the linear genome through addition of the third dimension...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27807141/structural-and-functional-consequences-of-a-disease-mutation-in-the-telomere-protein-tpp1
#13
Kamlesh Bisht, Eric M Smith, Valerie M Tesmer, Jayakrishnan Nandakumar
Telomerase replicates chromosome ends to facilitate continued cell division. Mutations that compromise telomerase function result in stem cell failure diseases, such as dyskeratosis congenita (DC). One such mutation (K170Δ), residing in the telomerase-recruitment factor TPP1, provides an excellent opportunity to structurally, biochemically, and genetically dissect the mechanism of such diseases. We show through site-directed mutagenesis and X-ray crystallography that this TPP1 disease mutation deforms the conformation of two critical amino acids of the TEL [TPP1's glutamate (E) and leucine-rich (L)] patch, the surface of TPP1 that binds telomerase...
November 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27802612/computer-simulations-of-melts-of-randomly-branching-polymers
#14
Angelo Rosa, Ralf Everaers
Randomly branching polymers with annealed connectivity are model systems for ring polymers and chromosomes. In this context, the branched structure represents transient folding induced by topological constraints. Here we present computer simulations of melts of annealed randomly branching polymers of 3 ≤ N ≤ 1800 segments in d = 2 and d = 3 dimensions. In all cases, we perform a detailed analysis of the observed tree connectivities and spatial conformations. Our results are in excellent agreement with an asymptotic scaling of the average tree size of R ∼ N(1/d), suggesting that the trees behave as compact, territorial fractals...
October 28, 2016: Journal of Chemical Physics
https://www.readbyqxmd.com/read/27798106/dna-methylation-independent-removable-insulator-controls-chromatin-remodeling-at-the-hoxa-locus-via-retinoic-acid-signaling
#15
Ko Ishihara, Masafumi Nakamoto, Mitsuyoshi Nakao
Chromatin insulators partition the genome into functional units to control gene expression, particularly in complex chromosomal regions. The CCCTC-binding factor (CTCF) is an insulator-binding protein that functions in transcriptional regulation and higher-order chromatin formation. Variable CTCF-binding sites have been identified to be cell type-specific partly due to differential DNA methylation. Here, we show that DNA methylation-independent removable CTCF insulator is responsible for retinoic acid (RA)-mediated higher-order chromatin remodeling in the human HOXA gene locus...
October 24, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27791029/crystal-structure-of-the-dna-binding-domain-of-the-transcription-factor-t-bet-suggests-simultaneous-recognition-of-distant-genome-sites
#16
Ce Feng Liu, Gabriel S Brandt, Quyen Q Hoang, Natalia Naumova, Vanja Lazarevic, Eun Sook Hwang, Job Dekker, Laurie H Glimcher, Dagmar Ringe, Gregory A Petsko
The transcription factor T-bet (Tbox protein expressed in T cells) is one of the master regulators of both the innate and adaptive immune responses. It plays a central role in T-cell lineage commitment, where it controls the TH1 response, and in gene regulation in plasma B-cells and dendritic cells. T-bet is a member of the Tbox family of transcription factors; however, T-bet coordinately regulates the expression of many more genes than other Tbox proteins. A central unresolved question is how T-bet is able to simultaneously recognize distant Tbox binding sites, which may be located thousands of base pairs away...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27789693/3dsnp-a-database-for-linking-human-noncoding-snps-to-their-three-dimensional-interacting-genes
#17
Yiming Lu, Cheng Quan, Hebing Chen, Xiaochen Bo, Chenggang Zhang
The vast noncoding portion of the human genome harbors a rich array of functional elements and disease-causing regulatory variants. Recent high-throughput chromosome conformation capture studies have outlined the principles of these elements interacting and regulating the expression of distal target genes through three-dimensional (3D) chromatin looping. Here we present 3DSNP, an integrated database for annotating human noncoding variants by exploring their roles in the distal interactions between genes and regulatory elements...
October 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27788031/quantification-of-radiation-biomarkers-in-leukocytes-of-breast-cancer-patients-treated-with-different-modalities-of-3d-crt-or-imrt
#18
Sebastian Zahnreich, Anne Ebersberger, Heiko Karle, Bernd Kaina, Heinz Schmidberger
The goal of this study was to determine whether the quantification of radiation biomarkers in peripheral leukocytes of 111 breast cancer patients after adjuvant treatment with different modalities of three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) revealed any difference in the patients' radiation burden by out-of-field doses and an associated risk of second malignancies. Whole-breast radiation therapy was performed by 3D-CRT using either a hard wedge (n = 32) or a virtual wedge (n = 49) at dose rates of 3 and 6 Gy per min each...
October 27, 2016: Radiation Research
https://www.readbyqxmd.com/read/27770354/chromatin-conformation-capture-based-analysis-of-nuclear-architecture
#19
Stefan Grob, Ueli Grossniklaus
Nuclear organization and higher-order chromosome structure in interphase nuclei are thought to have important effects on fundamental biological processes, including chromosome condensation, replication, and transcription. Until recently, however, nuclear organization could only be analyzed microscopically. The development of chromatin conformation capture (3C)-based techniques now allows a detailed look at chromosomal architecture from the level of individual loci to the entire genome. Here we provide a robust Hi-C protocol, allowing the analysis of nuclear organization in nuclei from different wild-type and mutant plant tissues...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27768699/multiple-pairwise-analysis-of-non-homologous-centromere-coupling-reveals-preferential-chromosome-size-dependent-interactions-and-a-role-for-bouquet-formation-in-establishing-the-interaction-pattern
#20
Philippe Lefrançois, Beth Rockmill, Pingxing Xie, G Shirleen Roeder, Michael Snyder
During meiosis, chromosomes undergo a homology search in order to locate their homolog to form stable pairs and exchange genetic material. Early in prophase, chromosomes associate in mostly non-homologous pairs, tethered only at their centromeres. This phenomenon, conserved through higher eukaryotes, is termed centromere coupling in budding yeast. Both initiation of recombination and the presence of homologs are dispensable for centromere coupling (occurring in spo11 mutants and haploids induced to undergo meiosis) but the presence of the synaptonemal complex (SC) protein Zip1 is required...
October 2016: PLoS Genetics
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