Read by QxMD icon Read


Camilla Björkegren, Laura Baranello
Although our knowledge of chromatin organization has advanced significantly in recent years, much about the relationships between different features of genome architecture is still unknown. Folding of mammalian genomes into spatial domains is thought to depend on architectural proteins, other DNA-binding proteins, and different forms of RNA. In addition, emerging evidence points towards the possibility that the three-dimensional organisation of the genome is controlled by DNA topology. In this scenario, cohesin, CCCTC-binding factor (CTCF), transcription, DNA supercoiling, and topoisomerases are integrated to dictate different layers of genome organization, and the contribution of all four to gene control is an important direction of future studies...
March 16, 2018: International Journal of Molecular Sciences
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
Danielle A Chisolm, Amy S Weinmann
The nutrient environment and metabolism play a dynamic role in cellular differentiation and research is elucidating the mechanisms that contribute to this process. Metabolites serve as an effective bridge that helps to translate information about nutrient states into specific interpretations of the genome. Part of this activity relates to the role for metabolites in regulating epigenetic processes as well as a newly appreciated role for metabolites in the regulation of genome organization. In this review, we will highlight recent research that has defined roles for metabolism in the organization and interpretation of the genome and how this influences cellular differentiation decisions...
March 8, 2018: Current Opinion in Immunology
Shannan D Washington, Samantha I Edenfield, Caroline Lieux, Zachary L Watson, Sean M Taasan, Adit Dhummakupt, David C Bloom, Donna M Neumann
Herpes Simplex Virus 1 (HSV-1) establishes a lifelong latent infection in host peripheral neurons including the neurons of the trigeminal ganglia (TG). HSV-1 can reactivate from neurons to cause recurrent infection. During latency, the insulator protein CTCF occupies DNA binding sites on the HSV-1 genome and these sites have been previously characterized as functional enhancer-blocking insulators. Previously, CTCF was found to be dissociated from wild type virus post-reactivation but not in mutants that do not reactivate, indicating that CTCF eviction may also be an important component of reactivation...
March 7, 2018: Journal of Virology
Jialiang Huang, Kailong Li, Wenqing Cai, Xin Liu, Yuannyu Zhang, Stuart H Orkin, Jian Xu, Guo-Cheng Yuan
Recent studies have highlighted super-enhancers (SEs) as important regulatory elements for gene expression, but their intrinsic properties remain incompletely characterized. Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers. Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants...
March 5, 2018: Nature Communications
Steven E Pierce, Trevor Tyson, Alix Booms, Jordan Prahl, Gerhard A Coetzee
In genome-wide association studies of complex diseases, many risk polymorphisms are found to lie in non-coding DNA and likely confer risk through allele-dependent differences in gene regulatory elements. However, because distal regulatory elements can alter gene expression at various distances on linear DNA, the identity of relevant genes is unknown for most risk loci. In Parkinson's disease, at least some genetic risk is likely intrinsic to a neuronal subpopulation of cells in the brain regions affected. In order to compare neuron-relevant methods of pairing risk polymorphisms to target genes as well as to further characterize a single-cell model of a neurodegenerative disease, we used the portionally-dopaminergic, neuronal, mesencephalic-derived cell line LUHMES to dissect differentiation-specific mechanisms of gene expression...
February 24, 2018: Neurobiology of Disease
Angela Sparago, Flavia Cerrato, Andrea Riccio
Background: Loss of paternal methylation (LOM) of the H19/IGF2 intergenic differentially methylated region ( H19/IGF2 :IG-DMR) causes alteration of H19/IGF2 imprinting and Silver-Russell syndrome (SRS). Recently, internal deletions of the H19/IGF2 :IG-DMR have been associated with LOM and SRS when present on the paternal chromosome. In contrast, previously described deletions, most of which cause gain of methylation (GOM) and Beckwith-Wiedemann syndrome (BWS) on maternal transmission, were consistently associated with normal methylation and phenotype if paternally inherited...
2018: Clinical Epigenetics
Vivek Behera, Perry Evans, Carolyne J Face, Nicole Hamagami, Laavanya Sankaranarayanan, Cheryl A Keller, Belinda Giardine, Kai Tan, Ross C Hardison, Junwei Shi, Gerd A Blobel
Single-nucleotide variants that underlie phenotypic variation can affect chromatin occupancy of transcription factors (TFs). To delineate determinants of in vivo TF binding and chromatin accessibility, we introduce an approach that compares ChIP-seq and DNase-seq data sets from genetically divergent murine erythroid cell lines. The impact of discriminatory single-nucleotide variants on TF ChIP signal enables definition at single base resolution of in vivo binding characteristics of nuclear factors GATA1, TAL1, and CTCF...
February 22, 2018: Nature Communications
Marta Christov, Abbe R Clark, Braden Corbin, Samy Hakroush, Eugene P Rhee, Hiroaki Saito, Dan Brooks, Eric Hesse, Mary Bouxsein, Niels Galjart, Ji Yong Jung, Peter Mundel, Harald Jüppner, Astrid Weins, Anna Greka
Progressive chronic kidney diseases (CKDs) are on the rise worldwide. However, the sequence of events resulting in CKD progression remain poorly understood. Animal models of CKD exploring these issues are confounded by systemic toxicities or surgical interventions to acutely induce kidney injury. Here we report the generation of a CKD mouse model through the inducible podocyte-specific ablation of an essential endogenous molecule, the chromatin structure regulator CCCTC-binding factor (CTCF), which leads to rapid podocyte loss (iCTCFpod-/-)...
February 22, 2018: JCI Insight
Chong Wang, Hufeng Zhou, Yong Xue, Jun Liang, Yohei Narita, Catherine Gerdt, Amy Y Zheng, Runsheng Jiang, Stephen Trudeau, Chih-Wen Peng, Benjamin Gewurz, Bo Zhao
Epstein-Barr virus nuclear antigen (EBNA) leader protein (EBNALP) is one of the first viral genes expressed upon B-cell infection. EBNALP is essential for EBV-mediated B cell immortalization. EBNALP is thought to function primarily by co-activaing EBNA2-mediated transcription. Chromatin immune precipitation followed by deep-sequencing (ChIP-seq) studies highlight that EBNALP frequently co-occupies DNA sites with host cell transcription factors (TFs), in particular EP300, implicating a broader role in transcription regulation...
February 21, 2018: Journal of Virology
Valentina Miano, Giulio Ferrero, Valentina Rosti, Eleonora Manitta, Jamal Elhasnaoui, Giulia Basile, Michele De Bortoli
Estrogen receptor-α (ERα) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we demonstrated that even in absence of ligands ERα (apoERα) binds chromatin sites where it regulates transcription of several protein-coding and lncRNA genes. Noteworthy, apoERα-regulated lncRNAs marginally overlap estrogen-induced transcripts, thus representing a new signature of luminal BC genes. By the analysis of H3K27ac enrichment in hormone-deprived MCF-7 cells, we defined a set of Super Enhancers (SEs) occupied by apoERα, including one mapped in proximity of the DSCAM-AS1 lncRNA gene...
February 16, 2018: International Journal of Molecular Sciences
Shuvra Shekhar Roy, Ananda Kishore Mukherjee, Shantanu Chowdhury
Over the last 15 years, development of chromosome conformation capture (3C) and its subsequent high-throughput variants in conjunction with the fast development of sequencing technology has allowed investigators to generate large volumes of data giving insights into the spatial three-dimensional (3D) architecture of the genome. This huge data has been analyzed and validated using various statistical, mathematical, genomics, and biophysical tools in order to examine the chromosomal interaction patterns, understand the organization of the chromosome, and find out functional implications of the interactions...
February 20, 2018: Human Genomics
Shannan D Washington, Farhana Musarrat, Monica K Ertel, Gregory L Backes, Donna M Neumann
There are seven conserved CTCF binding domains in the HSV-1 genome. These binding sites individually flank the LAT and the IE gene regions, suggesting that CTCF insulators differentially control transcriptional domains in HSV-1 latency. In this work, we show that two CTCF binding motifs in HSV-1 display enhancer-blocking in a cell-type specific manner. We found that CTCF binding to the latent HSV-1 genome was LAT-dependent and the quantity of bound CTCF was site-specific. Following reactivation, CTCF eviction was dynamic suggesting each CTCF site was independently regulated...
February 7, 2018: Journal of Virology
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
Matthew T Mawhinney, Runcong Liu, Fang Lu, Jasna Maksimoska, Kevin Damico, Ronen Marmorstein, Paul M Lieberman, Brigita Urbanc
The CTCF protein has emerged as a key architectural protein involved in genome organization. Although hypothesized to initiate DNA looping, direct evidence of CTCF-induced DNA loop formation is still missing. Several studies have shown that the eleven zinc finger (11 ZF) domain of CTCF is actively involved in DNA binding. We here use atomic force microscopy (AFM) to examine the effect of the 11 zinc finger (ZF) domain comprising residues 266-579 (11 ZF CTCF) and the 3 ZF domain comprising residues 402-494 (6-8 ZF CTCF) of human CTCF on the DNA morphology...
January 30, 2018: Journal of Molecular Biology
Meng Wang, Lilah Fones, John W Cave
Tyrosine hydroxylase (Th) encodes the rate-limiting enzyme in catecholamine biosynthesis, and the regulation of its transcription is critical for the specification and maintenance of catecholaminergic neuron phenotypes. For many genes, regulatory genomic DNA sequences that are upstream of the proximal promoter control expression levels as well as region-specific expression patterns. The regulatory architecture of the genomic DNA upstream of the Th proximal promoter, however, is poorly understood. In this study, we examined the 11 kb upstream nucleotide sequence of Th from nine mammalian species and identified five highly conserved regions...
February 5, 2018: Molecular Neurobiology
Xiang Zhao, Dan Li, Dandan Huang, Huajie Song, Hong Mei, Erhu Fang, Xiaojing Wang, Feng Yang, Liduan Zheng, Kai Huang, Qiangsong Tong
Neuroblastoma (NB) is the most common extracranial tumor in childhood. Recent studies have implicated the emerging roles of long noncoding RNAs (lncRNAs) in tumorigenesis and aggressiveness. However, the functions and targets of risk-associated lncRNAs in NB progression still remain to be determined. Herein, through mining of public microarray datasets, we identify lncRNA forkhead box D3 antisense RNA 1 (FOXD3-AS1) as an independent prognostic marker for favorable outcome of NB patients. FOXD3-AS1 is downregulated in NB tissues and cell lines, and ectopic expression of FOXD3-AS1 induces neuronal differentiation and decreases the aggressiveness of NB cells in vitro and in vivo...
December 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Kamel Jabbari, Peter Heger, Ranu Sharma, Thomas Wiehe
The CCCTC-binding factor (CTCF) is multi-functional, ubiquitously expressed, and highly conserved from Drosophila to human. It has important roles in transcriptional insulation and the formation of a high-dimensional chromatin structure. CTCF has a paralog called "Brother of Regulator of Imprinted Sites" (BORIS) or "CTCF-like" (CTCFL). It binds DNA at sites similar to those of CTCF. However, the expression profiles of the two proteins are quite different. We investigated the evolutionary trajectories of the two proteins after the duplication event using a phylogenomic and interactomic approach...
January 30, 2018: Life
Lori L O'Brien, Qiuyu Guo, Emad Bahrami-Samani, Joo-Seop Park, Sean M Hasso, Young-Jin Lee, Alan Fang, Albert D Kim, Jinjin Guo, Trudy M Hong, Kevin A Peterson, Scott Lozanoff, Ramya Raviram, Bing Ren, Ben Fogelgren, Andrew D Smith, Anton Valouev, Andrew P McMahon
Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs...
January 29, 2018: PLoS Genetics
Jiang Liu, Zhaoli Ding, Guimei Li, Li Tang, Yu Xu, Huayou Luo, Jinhua Yi, Youwang Lu, Rui Mao, Qiong Nan, Li Ren, Tong Zhang, Kunhua Wang
To date, the sensitivity of currently available biomarkers based on the methylation of gene promoters is suboptimal for detecting adenomas and early-stage colorectal cancer (CRC). We aimed to develop biomarkers with methylated DNA binding sites of the multifunctional transcriptional factor CTCF for early detection of CRC. Using combined analyses of genome-wide occupation and the methylation profile of CTCF-binding sites, we identified candidate CTCF-binding sites. Then, we applied methylation-sensitive high-resolution melting (MS-HRM) and mass spectrometry analysis to screen and validate these candidate sites in diverse sample sets...
December 26, 2017: Oncotarget
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"