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topologically associated domains

Paulo P Amaral, Tommaso Leonardi, Namshik Han, Emmanuelle Viré, Dennis K Gascoigne, Raúl Arias-Carrasco, Magdalena Büscher, Luca Pandolfini, Anda Zhang, Stefano Pluchino, Vinicius Maracaja-Coutinho, Helder I Nakaya, Martin Hemberg, Ramin Shiekhattar, Anton J Enright, Tony Kouzarides
BACKGROUND: The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider promoter conservation and positional conservation as indicators of functional commonality. RESULTS: We identify 665 conserved lncRNA promoters in mouse and human that are preserved in genomic position relative to orthologous coding genes...
March 15, 2018: Genome Biology
Yan Yan, Yue Ding, Fenfei Leng, David Dunlap, Laura Finzi
Supercoiling can alter the form and base pairing of the double helix and directly impact protein binding. More indirectly, changes in protein binding and the stress of supercoiling also influence the thermodynamic stability of regulatory, protein-mediated loops and shift the equilibria of fundamental DNA/chromatin transactions. For example, supercoiling affects the hierarchical organization and function of chromatin in topologically associating domains (TADs) in both eukaryotes and bacteria. On the other hand, a protein-mediated loop in DNA can constrain supercoiling within a plectonemic structure...
March 10, 2018: Nucleic Acids Research
Hao Sun, Frederic Lagarrigue, Alexandre R Gingras, Zhichao Fan, Klaus Ley, Mark H Ginsberg
Integrin activation regulates adhesion, extracellular matrix assembly, and cell migration, thereby playing an indispensable role in development and in many pathological processes. A proline mutation in the central integrin β3 transmembrane domain (TMD) creates a flexible kink that uncouples the topology of the inner half of the TMD from the outer half. In this study, using leukocyte integrin α4β7, which enables development of gut-associated lymphoid tissue (GALT), we examined the biological effect of such a proline mutation and report that it impairs agonist-induced talin-mediated activation of integrin α4β7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration...
March 13, 2018: Journal of Cell Biology
Ezequiel Nazer, Ryan K Dale, Madoka Chinen, Behram Radmanesh, Elissa P Lei
Drosophila Argonaute2 (AGO2) has been shown to regulate expression of certain loci in an RNA interference (RNAi)-independent manner, but its genome-wide function on chromatin remains unknown. Here, we identified the nuclear scaffolding protein LaminB as a novel interactor of AGO2. When either AGO2 or LaminB are depleted in Kc cells, similar transcription changes are observed genome-wide. In particular, changes in expression occur mainly in active or potentially active chromatin, both inside and outside LaminB-associated domains (LADs)...
March 12, 2018: PLoS Genetics
Anas Z Abidin, Adora M DSouza, Mahesh B Nagarajan, Lu Wang, Xing Qiu, Giovanni Schifitto, Axel Wismüller
HIV is capable of invading the brain soon after seroconversion. This ultimately can lead to deficits in multiple cognitive domains commonly referred to as HIV-associated neurocognitive disorders (HAND). Clinical diagnosis of such deficits requires detailed neuropsychological assessment but clinical signs may be difficult to detect during asymptomatic injury of the central nervous system (CNS). Therefore neuroimaging biomarkers are of particular interest in HAND. In this study, we constructed brain connectivity profiles of 40 subjects (20 HIV positive subjects and 20 age-matched seronegative controls) using two different methods: a non-linear mutual connectivity analysis approach and a conventional method based on Pearson's correlation...
2018: NeuroImage: Clinical
Ibai Irastorza-Azcarate, Rafael D Acemel, Juan J Tena, Ignacio Maeso, José Luis Gómez-Skarmeta, Damien P Devos
The use of 3C-based methods has revealed the importance of the 3D organization of the chromatin for key aspects of genome biology. However, the different caveats of the variants of 3C techniques have limited their scope and the range of scientific fields that could benefit from these approaches. To address these limitations, we present 4Cin, a method to generate 3D models and derive virtual Hi-C (vHi-C) heat maps of genomic loci based on 4C-seq or any kind of 4C-seq-like data, such as those derived from NG Capture-C...
March 9, 2018: PLoS Computational Biology
Quentin Szabo, Daniel Jost, Jia-Ming Chang, Diego I Cattoni, Giorgio L Papadopoulos, Boyan Bonev, Tom Sexton, Julian Gurgo, Caroline Jacquier, Marcelo Nollmann, Frédéric Bantignies, Giacomo Cavalli
Deciphering the rules of genome folding in the cell nucleus is essential to understand its functions. Recent chromosome conformation capture (Hi-C) studies have revealed that the genome is partitioned into topologically associating domains (TADs), which demarcate functional epigenetic domains defined by combinations of specific chromatin marks. However, whether TADs are true physical units in each cell nucleus or whether they reflect statistical frequencies of measured interactions within cell populations is unclear...
February 2018: Science Advances
Moses J Leavens, Melisa M Cherney, Michaela L Finnegan, Bruce E Bowler
Previous work with the four-helix-bundle protein cytochrome c' from Rhodopseudomonas palustris using histidine-heme loop formation methods revealed fold-specific deviations from random coil behavior in its denatured state ensemble. To examine the generality of this finding, we extend this work to a three-helix-bundle polypeptide, the second ubiquitin-associated domain, UBA(2), of the human DNA excision repair protein. We use yeast iso-1-cytochrome c as a scaffold, fusing the UBA(2) domain at the N-terminus of iso-1-cytochrome c...
February 26, 2018: Biochemistry
Qian Bian, Erika C Anderson, Katjuša Brejc, Barbara J Meyer
The function of chromatin modification in establishing higher-order chromosome structure during gene regulation has been elusive. We dissected the machinery and mechanism underlying the enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during Caenorhabditis elegans dosage compensation and discovered a key role for H4K20me1 in regulating X-chromosome topology and chromosome-wide gene expression. Structural and functional analysis of the dosage compensation complex (DCC) subunit DPY-21 revealed a novel Jumonji C demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals...
February 22, 2018: Cold Spring Harbor Symposia on Quantitative Biology
Gangqing Hu, Kairong Cui, Difeng Fang, Satoshi Hirose, Xun Wang, Darawalee Wangsa, Wenfei Jin, Thomas Ried, Pentao Liu, Jinfang Zhu, Ellen V Rothenberg, Keji Zhao
How chromatin reorganization coordinates differentiation and lineage commitment from hematopoietic stem and progenitor cells (HSPCs) to mature immune cells has not been well understood. Here, we carried out an integrative analysis of chromatin accessibility, topologically associating domains, AB compartments, and gene expression from HSPCs to CD4+ CD8+ T cells. We found that abrupt genome-wide changes at all three levels of chromatin organization occur during the transition from double-negative stage 2 (DN2) to DN3, accompanying the T lineage commitment...
February 20, 2018: Immunity
Bruce H Howard, Tazuko H Hirai, Valya R Russanova
Substantial evidence has accumulated linking epigenome change to alterations in stem cell function during postnatal development and aging. Yet much remains to be learned about causal relationships, and large gaps remain in our understanding of epigenome-transcriptome interactions. Here we investigate structural features of large histone H3K27me3-enriched regions in human stem cell-like monocytes and their dendritic cell derivatives, where the H3K27me3 modification is considered to demarcate Polycomb (PcG) domains...
2018: PloS One
Maarten G K Ghequire, Susan K Buchanan, René De Mot
Bacteria host an arsenal of antagonism-mediating molecules to combat for ecologic space. Bacteriocins represent a pivotal group of secreted antibacterial peptides and proteins assisting in this fight, mainly eliminating relatives. Colicin M, a model for peptidoglycan-interfering bacteriocins in Gram-negative bacteria, appears to be part of a set of polymorphic toxins equipped with such a catalytic domain (ColM) targeting lipid II. Diversifying recombination has enabled parasitism of different receptors and has also given rise to hybrid bacteriocins in which ColM is associated with another toxin module...
February 13, 2018: MBio
Simon Staubach, Andrea Wenzel, Bodo B Beck, Markus M Rinschen, Stefan Müller, Franz-Georg Hanisch
Autosomal dominant tubulointerstitial kidney disease associated to the MUC1 gene (ADTKD-MUC1; formerly MCKD1) belongs to a heterogenous group of rare hereditary kidney diseases that is prototypically caused by frameshift mutations in the MUC1 repeat domain. The mutant MUC1(insC) lacks the transmembrane domaine, exhibits aberant cellular topology and hence might gain a function during the pathological process. To get insight into potential pathomechanisms we performed differential proteomics of extracellular vesicles shed by renal epithelia into the urine of patients...
February 13, 2018: Proteomics
Federico Comoglio, Hyun Jung Park, Stefan Schoenfelder, Iros Barozzi, Daniel Bode, Peter Fraser, Anthony R Green
Thrombopoietin (TPO) is a critical cytokine regulating hematopoietic stem cell maintenance and differentiation into the megakaryocytic lineage. However, the transcriptional and chromatin dynamics elicited by TPO signaling are poorly understood. Here, we study the immediate early transcriptional and cis-regulatory responses to TPO in hematopoietic stem/progenitor cells (HSPCs) and use this paradigm of cytokine signaling to chromatin to dissect the relation between cis- regulatory activity and chromatin architecture...
February 2, 2018: Genome Research
Yanjian Li, Yi He, Zhengyu Liang, Yang Wang, Fengling Chen, Mohamed Nadhir Djekidel, Guipeng Li, Xu Zhang, Shuqin Xiang, Zejun Wang, Juntao Gao, Michael Q Zhang, Yang Chen
Chromatin conformation plays a key role in regulating gene expression and controlling cell differentiation. However, the whole-genome chromatin conformation changes that occur during leukemia cell differentiation are poorly understood. Here, we characterized the changes in chromatin conformation, histone states, chromatin accessibility, and gene expression using an all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation model. The results showed that the boundaries of topological associated domains (TADs) were stable during differentiation; however, the chromatin conformations within several specific TADs were obviously changed...
February 8, 2018: Cell Death & Disease
Petros Kolovos, Rutger W W Brouwer, Christel E M Kockx, Michael Lesnussa, Nick Kepper, Jessica Zuin, A M Ali Imam, Harmen J G van de Werken, Kerstin S Wendt, Tobias A Knoch, Wilfred F J van IJcken, Frank Grosveld
Chromosome conformation capture (3C) and its derivatives (e.g., 4C, 5C and Hi-C) are used to analyze the 3D organization of genomes. We recently developed targeted chromatin capture (T2C), an inexpensive method for studying the 3D organization of genomes, interactomes and structural changes associated with gene regulation, the cell cycle, and cell survival and development. Here, we present the protocol for T2C based on capture, describing all experimental steps and bio-informatic tools in full detail. T2C offers high resolution, a large dynamic interaction frequency range and a high signal-to-noise ratio...
March 2018: Nature Protocols
Yixiao Gong, Charalampos Lazaris, Theodore Sakellaropoulos, Aurelie Lozano, Prabhanjan Kambadur, Panagiotis Ntziachristos, Iannis Aifantis, Aristotelis Tsirigos
The metazoan genome is compartmentalized in areas of highly interacting chromatin known as topologically associating domains (TADs). TADs are demarcated by boundaries mostly conserved across cell types and even across species. However, a genome-wide characterization of TAD boundary strength in mammals is still lacking. In this study, we first use fused two-dimensional lasso as a machine learning method to improve Hi-C contact matrix reproducibility, and, subsequently, we categorize TAD boundaries based on their insulation score...
February 7, 2018: Nature Communications
Kelin Xia
In this paper, we introduce sequence-based multiscale modeling for biomolecular data analysis. We employ spectral clustering method in our modeling and reveal the difference between sequence-based global scale clustering and local scale clustering. Essentially, two types of distances, i.e., Euclidean (or spatial) distance and genomic (or sequential) distance, can be used in data clustering. Clusters from sequence-based global scale models optimize spatial distances, meaning spatially adjacent loci are more likely to be assigned into the same cluster...
2018: PloS One
Sarah Rennie, Maria Dalby, Lucas van Duin, Robin Andersson
Transcriptional regulation is tightly coupled with chromosomal positioning and three-dimensional chromatin architecture. However, it is unclear what proportion of transcriptional activity is reflecting such organisation, how much can be informed by RNA expression alone and how this impacts disease. Here, we develop a computational transcriptional decomposition approach separating the proportion of expression associated with genome organisation from independent effects not directly related to genomic positioning...
February 5, 2018: Nature Communications
Yun-Ji Shin, Ulrike Vavra, Christiane Veit, Richard Strasser
A great number of soluble and integral membrane proteins fold in the endoplasmic reticulum (ER) with the help of chaperones and folding factors. Despite these efforts, protein folding is intrinsically error prone and amino acid changes, alterations in posttranslational modifications or cellular stress can cause protein misfolding. Folding-defective non-native proteins are cleared from the ER and typically undergo ER-associated degradation (ERAD). Here, we investigated whether different misfolded glycoproteins require the same set of ERAD factors and are directed to HRD1 complex-mediated degradation in plants...
February 3, 2018: Plant Journal: for Cell and Molecular Biology
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