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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
Amit Pande, Jürgen Brosius, Izabela Makalowska, Wojciech Makalowski, Carsten A Raabe
Proximal promoter regions (PPR) are heavily transcribed yielding different types of small RNAs. The act of transcription within PPRs might regulate downstream gene expression via transcriptional interference (TI). For analysis, we investigated capped and polyadenylated small RNA transcripts within PPRs of human RefSeq genes in eight different cell lines. Transcripts of our datasets overlapped with experimentally determined transcription factor binding sites (TFBS). For TFBSs intersected by these small RNA transcripts, we established negative correlation of sRNA expression levels and transcription factor (TF) DNA binding affinities; suggesting that the transcripts acted via TI...
January 4, 2018: Nucleic Acids Research
Ruobing Jia, Peiwei Chai, He Zhang, Xianqun Fan
Exploring gene function is critical for understanding the complexity of life. DNA sequences and the three-dimensional organization of chromatin (chromosomal interactions) are considered enigmatic factors underlying gene function, and interactions between two distant fragments can regulate transactivation activity via mediator proteins. Thus, a series of chromosome conformation capture techniques have been developed, including chromosome conformation capture (3C), circular chromosome conformation capture (4C), chromosome conformation capture carbon copy (5C), and high-resolution chromosome conformation capture (Hi-C)...
November 17, 2017: Molecular Cancer
Asa Thibodeau, Eladio J Márquez, Dong-Guk Shin, Paola Vera-Licona, Duygu Ucar
Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays...
October 31, 2017: Scientific Reports
Y L Orlov, O Thierry, A G Bogomolov, A V Tsukanov, E V Kulakova, E R Galieva, A O Bragin, G Li
The study spatial chromosome structure and chromosome folding in the interphase cell nucleus is an important challenge of world science. Detection of eukaryotic genome regions that physically interact with each other could be done by modern sequencing technologies. A basic method of chromosome folding by total sequencing of contacting DNA fragments is HI-C. Long-range chromosomal interactions play an important role in gene transcription and regulation. The study of chromosome interactions, 3D (three-dimensional) genome structure and its effect on gene transcription allows revealing fundamental biological processes from a viewpoint of structural regulation and are important for cancer research...
October 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
Peng Li, Suman Mitra, Rosanne Spolski, Jangsuk Oh, Wei Liao, Zhonghui Tang, Fei Mo, Xingwang Li, Erin E West, Daniel Gromer, Jian-Xin Lin, Chengyu Liu, Yijun Ruan, Warren J Leonard
Cytokines critically control immune responses, but how regulatory programs are altered to allow T cells to differentially respond to distinct cytokine stimuli remains poorly understood. Here, we have globally analyzed enhancer elements bound by IL-2-activated STAT5 and IL-21-activated STAT3 in T cells and identified Il2ra as the top-ranked gene regulated by an IL-2-activated STAT5-bound superenhancer and one of the top genes regulated by STAT3-bound superenhancers. Moreover, we found that STAT5 binding was rapidly superenriched at genes highly induced by IL-2 and that IL-2-activated STAT5 binding induces new and augmented chromatin interactions within superenhancer-containing genes...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
Yaping Liu, Abhishek Sarkar, Pouya Kheradpour, Jason Ernst, Manolis Kellis
BACKGROUND: Recombination rate is non-uniformly distributed across the human genome. The variation of recombination rate at both fine and large scales cannot be fully explained by DNA sequences alone. Epigenetic factors, particularly DNA methylation, have recently been proposed to influence the variation in recombination rate. RESULTS: We study the relationship between recombination rate and gene regulatory domains, defined by a gene and its linked control elements...
October 20, 2017: Genome Biology
Hui Zhang, Feifei Li, Yan Jia, Bingxiang Xu, Yiqun Zhang, Xiaoli Li, Zhihua Zhang
High-throughput chromosome conformation capture (3C) technologies, such as Hi-C, have made it possible to survey 3D genome structure. However, obtaining 3D profiles at kilobase resolution at low cost remains a major challenge. Therefore, we herein present an algorithm for precise identification of chromatin interaction sites at kilobase resolution from MNase-seq data, termed chromatin interaction site detector (CISD), and a CISD-based chromatin loop predictor (CISD_loop) that predicts chromatin-chromatin interactions (CCIs) from low-resolution Hi-C data...
December 15, 2017: Nucleic Acids Research
Caleb A Lareau, Martin J Aryee
Summary: The three-dimensional architecture of DNA within the nucleus is a key determinant of interactions between genes, regulatory elements, and transcriptional machinery. As a result, differences in DNA looping structure are associated with variation in gene expression and cell state. To systematically assess changes in DNA looping architecture between samples, we introduce diffloop, an R/Bioconductor package that provides a suite of functions for the quality control, statistical testing, annotation, and visualization of DNA loops...
September 29, 2017: Bioinformatics
Gamze Gürsoy, Yun Xu, Amy L Kenter, Jie Liang
Conformation capture technologies measure frequencies of interactions between chromatin regions. However, understanding gene-regulation require knowledge of detailed spatial structures of heterogeneous chromatin in cells. Here we describe the nC-SAC (n-Constrained-Self Avoiding Chromatin) method that transforms experimental interaction frequencies into 3D ensembles of chromatin chains. nC-SAC first distinguishes specific from non-specific interaction frequencies, then generates 3D chromatin ensembles using identified specific interactions as spatial constraints...
November 16, 2017: Nucleic Acids Research
Binhua Tang, Xiaolong Cheng, Yunlong Xi, Zixin Chen, Yufan Zhou, Victor X Jin
Recent sequence-based profiling technologies such as high-throughput sequencing to detect fragment nucleotide sequence (Hi-C) and chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) have revolutionized the field of three-dimensional (3D) chromatin architecture. It is now recognized that human genome functions as folded 3D chromatin units and looping paradigm is the basic principle of gene regulation. To better interpret the 3D data dramatically accumulating in past five years and to gain deep biological insights, huge efforts have been made in developing novel quantitative analysis methods...
September 8, 2017: Genes
Joshua S Martin, Zheng Xu, Alex P Reiner, Karen L Mohlke, Patrick Sullivan, Bing Ren, Ming Hu, Yun Li
Motivation: High throughput chromatin conformation capture (3C) technologies, such as Hi-C and ChIA-PET, have the potential to elucidate the functional roles of non-coding variants. However, most of published genome-wide unbiased chromatin organization studies have used cultured cell lines, limiting their generalizability. Results: We developed a web browser, HUGIn, to visualize Hi-C data generated from 21 human primary tissues and cell lines. HUGIn enables assessment of chromatin contacts both constitutive across and specific to tissue(s) and/or cell line(s) at any genomic loci, including GWAS SNPs, eQTLs and cis-regulatory elements, facilitating the understanding of both GWAS and eQTL results and functional genomics data...
December 1, 2017: Bioinformatics
Thandiswa Ngcungcu, Martin Oti, Jan C Sitek, Bjørn I Haukanes, Bolan Linghu, Robert Bruccoleri, Tomasz Stokowy, Edward J Oakeley, Fan Yang, Jiang Zhu, Marc Sultan, Joost Schalkwijk, Ivonne M J J van Vlijmen-Willems, Charlotte von der Lippe, Han G Brunner, Kari M Ersland, Wayne Grayson, Stine Buechmann-Moller, Olav Sundnes, Nanguneri Nirmala, Thomas M Morgan, Hans van Bokhoven, Vidar M Steen, Peter R Hull, Joseph Szustakowski, Frank Staedtler, Huiqing Zhou, Torunn Fiskerstrand, Michele Ramsay
Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis...
May 4, 2017: American Journal of Human Genetics
Xingwang Li, Oscar Junhong Luo, Ping Wang, Meizhen Zheng, Danjuan Wang, Emaly Piecuch, Jacqueline Jufen Zhu, Simon Zhongyuan Tian, Zhonghui Tang, Guoliang Li, Yijun Ruan
Chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is a robust method for capturing genome-wide chromatin interactions. Unlike other 3C-based methods, it includes a chromatin immunoprecipitation (ChIP) step that enriches for interactions mediated by specific target proteins. This unique feature allows ChIA-PET to provide the functional specificity and higher resolution needed to detect chromatin interactions, which chromosome conformation capture (3C)/Hi-C approaches have not achieved. The original ChIA-PET protocol generates short paired-end tags (2 × 20 base pairs (bp)) to detect two genomic loci that are far apart on linear chromosomes but are in spatial proximity in the folded genome...
May 2017: Nature Protocols
Lisha Zhu, Kaiyu Jiang, Karstin Webber, Laiping Wong, Tao Liu, Yanmin Chen, James N Jarvis
BACKGROUND: The transcriptomes of peripheral blood cells in children with juvenile idiopathic arthritis (JIA) have distinct transcriptional aberrations that suggest impairment of transcriptional regulation. To gain a better understanding of this phenomenon, we studied known JIA genetic risk loci, the majority of which are located in non-coding regions, where transcription is regulated and coordinated on a genome-wide basis. We examined human neutrophils and CD4 primary T cells to identify genes and functional elements located within those risk loci...
March 14, 2017: Arthritis Research & Therapy
Galip Gürkan Yardımcı, William Stafford Noble
High-throughput assays for measuring the three-dimensional (3D) configuration of DNA have provided unprecedented insights into the relationship between DNA 3D configuration and function. Data interpretation from assays such as ChIA-PET and Hi-C is challenging because the data is large and cannot be easily rendered using standard genome browsers. An effective Hi-C visualization tool must provide several visualization modes and be capable of viewing the data in conjunction with existing, complementary data. We review five software tools that do not require programming expertise...
February 3, 2017: Genome Biology
Przemysław Szałaj, Zhonghui Tang, Paul Michalski, Michal J Pietal, Oscar J Luo, Michał Sadowski, Xingwang Li, Kamen Radew, Yijun Ruan, Dariusz Plewczynski
ChIA-PET is a high-throughput mapping technology that reveals long-range chromatin interactions and provides insights into the basic principles of spatial genome organization and gene regulation mediated by specific protein factors. Recently, we showed that a single ChIA-PET experiment provides information at all genomic scales of interest, from the high-resolution locations of binding sites and enriched chromatin interactions mediated by specific protein factors, to the low resolution of nonenriched interactions that reflect topological neighborhoods of higher-order chromosome folding...
December 2016: Genome Research
Jocelyn Choy, Melissa J Fullwood
Genomic DNA is dynamically associated with protein factors and folded to form chromatin fibers. The 3-dimensional (3D) configuration of the chromatin will enable the distal genetic elements to come into close proximity, allowing transcriptional regulation. Noncoding RNA can mediate the 3D structure of chromatin. Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) is a valuable and powerful technique in molecular biology which allows the study of unbiased, genome-wide de novo chromatin interactions with paired-end tags...
2017: Methods in Molecular Biology
Maxwell R Mumbach, Adam J Rubin, Ryan A Flynn, Chao Dai, Paul A Khavari, William J Greenleaf, Howard Y Chang
Genome conformation is central to gene control but challenging to interrogate. Here we present HiChIP, a protein-centric chromatin conformation method. HiChIP improves the yield of conformation-informative reads by over 10-fold and lowers the input requirement over 100-fold relative to that of ChIA-PET. HiChIP of cohesin reveals multiscale genome architecture with greater signal-to-background ratios than those of in situ Hi-C.
November 2016: Nature Methods
Guipeng Li, Yang Chen, Michael P Snyder, Michael Q Zhang
ChIA-PET2 is a versatile and flexible pipeline for analyzing different types of ChIA-PET data from raw sequencing reads to chromatin loops. ChIA-PET2 integrates all steps required for ChIA-PET data analysis, including linker trimming, read alignment, duplicate removal, peak calling and chromatin loop calling. It supports different kinds of ChIA-PET data generated from different ChIA-PET protocols and also provides quality controls for different steps of ChIA-PET analysis. In addition, ChIA-PET2 can use phased genotype data to call allele-specific chromatin interactions...
January 9, 2017: Nucleic Acids Research
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