DNA methylation at hepatitis B viral integrants is associated with methylation at flanking human genomic sequences.

Abstract:

:Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis.

journal_name

Genome Res

journal_title

Genome research

authors

Watanabe Y,Yamamoto H,Oikawa R,Toyota M,Yamamoto M,Kokudo N,Tanaka S,Arii S,Yotsuyanagi H,Koike K,Itoh F

doi

10.1101/gr.175240.114

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

328-37

issue

3

eissn

1088-9051

issn

1549-5469

pii

gr.175240.114

journal_volume

25

pub_type

杂志文章
  • ATAC-seq reveals regional differences in enhancer accessibility during the establishment of spatial coordinates in the Drosophila blastoderm.

    abstract::Establishment of spatial coordinates during Drosophila embryogenesis relies on differential regulatory activity of axis patterning enhancers. Concentration gradients of activator and repressor transcription factors (TFs) provide positional information to each enhancer, which in turn promotes transcription of a target ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.242362.118

    authors: Bozek M,Cortini R,Storti AE,Unnerstall U,Gaul U,Gompel N

    更新日期:2019-05-01 00:00:00

  • Most parsimonious reconciliation in the presence of gene duplication, loss, and deep coalescence using labeled coalescent trees.

    abstract::Accurate gene tree-species tree reconciliation is fundamental to inferring the evolutionary history of a gene family. However, although it has long been appreciated that population-related effects such as incomplete lineage sorting (ILS) can dramatically affect the gene tree, many of the most popular reconciliation me...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.161968.113

    authors: Wu YC,Rasmussen MD,Bansal MS,Kellis M

    更新日期:2014-03-01 00:00:00

  • Construction of an approximately 700-kb transcript map around the familial Mediterranean fever locus on human chromosome 16p13.3.

    abstract::We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequili...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.8.11.1172

    authors: Centola M,Chen X,Sood R,Deng Z,Aksentijevich I,Blake T,Ricke DO,Chen X,Wood G,Zaks N,Richards N,Krizman D,Mansfield E,Apostolou S,Liu J,Shafran N,Vedula A,Hamon M,Cercek A,Kahan T,Gumucio D,Callen DF,Richards

    更新日期:1998-11-01 00:00:00

  • Novel noncoding RNA from human Y distal heterochromatic block (Yq12) generates testis-specific chimeric CDC2L2.

    abstract::The human Y chromosome, because it is enriched in repetitive DNA, has been very intractable to genetic and molecular analyses. There is no previous evidence for developmental stage- and testis-specific transcription from the male-specific region of the Y (MSY). Here, we present evidence for the first time for a develo...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.5155706

    authors: Jehan Z,Vallinayagam S,Tiwari S,Pradhan S,Singh L,Suresh A,Reddy HM,Ahuja YR,Jesudasan RA

    更新日期:2007-04-01 00:00:00

  • Bacterial genomes as new gene homes: the genealogy of ORFans in E. coli.

    abstract::Differences in gene repertoire among bacterial genomes are usually ascribed to gene loss or to lateral gene transfer from unrelated cellular organisms. However, most bacteria contain large numbers of ORFans, that is, annotated genes that are restricted to a particular genome and that possess no known homologs. The uni...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2231904

    authors: Daubin V,Ochman H

    更新日期:2004-06-01 00:00:00

  • Copy-number-aware differential analysis of quantitative DNA sequencing data.

    abstract::Developments in microarray and high-throughput sequencing (HTS) technologies have resulted in a rapid expansion of research into epigenomic changes that occur in normal development and in the progression of disease, such as cancer. Not surprisingly, copy number variation (CNV) has a direct effect on HTS read densities...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.139055.112

    authors: Robinson MD,Strbenac D,Stirzaker C,Statham AL,Song J,Speed TP,Clark SJ

    更新日期:2012-12-01 00:00:00

  • Birth and expression evolution of mammalian microRNA genes.

    abstract::MicroRNAs (miRNAs) are major post-transcriptional regulators of gene expression, yet their origins and functional evolution in mammals remain little understood due to the lack of appropriate comparative data. Using RNA sequencing, we have generated extensive and comparable miRNA data for five organs in six species tha...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.140269.112

    authors: Meunier J,Lemoine F,Soumillon M,Liechti A,Weier M,Guschanski K,Hu H,Khaitovich P,Kaessmann H

    更新日期:2013-01-01 00:00:00

  • A first version of the Caenorhabditis elegans Promoterome.

    abstract::An important aspect of the development of systems biology approaches in metazoans is the characterization of expression patterns of nearly all genes predicted from genome sequences. Such "localizome" maps should provide information on where (in what cells or tissues) and when (at what stage of development or under wha...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2497604

    authors: Dupuy D,Li QR,Deplancke B,Boxem M,Hao T,Lamesch P,Sequerra R,Bosak S,Doucette-Stamm L,Hope IA,Hill DE,Walhout AJ,Vidal M

    更新日期:2004-10-01 00:00:00

  • Differential divergence of three human pseudoautosomal genes and their mouse homologs: implications for sex chromosome evolution.

    abstract::The human pseudoautosomal region 1 (PAR1) is essential for meiotic pairing and recombination, and its deletion causes male sterility. Comparative studies of human and mouse pseudoautosomal genes are valuable in charting the evolution of this interesting region, but have been limited by the paucity of genes conserved b...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.197001

    authors: Gianfrancesco F,Sanges R,Esposito T,Tempesta S,Rao E,Rappold G,Archidiacono N,Graves JA,Forabosco A,D'Urso M

    更新日期:2001-12-01 00:00:00

  • Nutritional control of mRNA isoform expression during developmental arrest and recovery in C. elegans.

    abstract::Nutrient availability profoundly influences gene expression. Many animal genes encode multiple transcript isoforms, yet the effect of nutrient availability on transcript isoform expression has not been studied in genome-wide fashion. When Caenorhabditis elegans larvae hatch without food, they arrest development in the...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.133587.111

    authors: Maxwell CS,Antoshechkin I,Kurhanewicz N,Belsky JA,Baugh LR

    更新日期:2012-10-01 00:00:00

  • Conservation, regulation, synteny, and introns in a large-scale C. briggsae-C. elegans genomic alignment.

    abstract::A new algorithm, WABA, was developed for doing large-scale alignments between genomic DNA of different species. WABA was used to align 8 million bases of Caenorhabditis briggsae genomic DNA against the entire 97-million-base Caenorhabditis elegans genome. The alignment, including C. briggsae homologs of 154 geneticall...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.10.8.1115

    authors: Kent WJ,Zahler AM

    更新日期:2000-08-01 00:00:00

  • Immune signatures correlate with L1 retrotransposition in gastrointestinal cancers.

    abstract::Long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons are normally suppressed in somatic tissues mainly due to DNA methylation and antiviral defense. However, the mechanism to suppress L1s may be disrupted in cancers, thus allowing L1s to act as insertional mutagens and cause genomic rearrangement and in...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.231837.117

    authors: Jung H,Choi JK,Lee EA

    更新日期:2018-08-01 00:00:00

  • Unamplified cap analysis of gene expression on a single-molecule sequencer.

    abstract::We report the development of a simplified cap analysis of gene expression (CAGE) protocol adapted for single-molecule sequencers that avoids second strand synthesis, ligation, digestion, and PCR. HeliScopeCAGE directly sequences the 3' end of cap trapped first-strand cDNAs. As with previous versions of CAGE, we better...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.115469.110

    authors: Kanamori-Katayama M,Itoh M,Kawaji H,Lassmann T,Katayama S,Kojima M,Bertin N,Kaiho A,Ninomiya N,Daub CO,Carninci P,Forrest AR,Hayashizaki Y

    更新日期:2011-07-01 00:00:00

  • Alternative approach to a heavy weight problem.

    abstract::Obesity is reaching epidemic proportions in developed countries and represents a significant risk factor for hypertension, heart disease, diabetes, and dyslipidemia. Splicing mutations constitute at least 14% of disease-causing mutations, thus implicating polymorphisms that affect splicing as likely candidates for dis...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.6661308

    authors: Goren A,Kim E,Amit M,Bochner R,Lev-Maor G,Ahituv N,Ast G

    更新日期:2008-02-01 00:00:00

  • A biometrical genome search in rats reveals the multigenic basis of blood pressure variation.

    abstract::A genome-wide search for multiple loci influencing salt-loaded systolic blood pressure (NaSBP) variation among 188 F2 progeny from a cross between the Brown-Norway and spontaneously hypertensive rat strains was pursued in an effort to gain insight into the polygenic basis of blood pressure regulation. The results sugg...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.5.2.164

    authors: Schork NJ,Krieger JE,Trolliet MR,Franchini KG,Koike G,Krieger EM,Lander ES,Dzau VJ,Jacob HJ

    更新日期:1995-09-01 00:00:00

  • Characterization and dynamics of pericentromere-associated domains in mice.

    abstract::Despite recent progress in genome topology knowledge, the role of repeats, which make up the majority of mammalian genomes, remains elusive. Satellite repeats are highly abundant sequences that cluster around centromeres, attract pericentromeric heterochromatin, and aggregate into nuclear chromocenters. These nuclear ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.186643.114

    authors: Wijchers PJ,Geeven G,Eyres M,Bergsma AJ,Janssen M,Verstegen M,Zhu Y,Schell Y,Vermeulen C,de Wit E,de Laat W

    更新日期:2015-07-01 00:00:00

  • Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs.

    abstract::Fetal liver intriguingly consists of hepatic parenchymal cells and hematopoietic stem/progenitor cells. Human fetal liver aged 22 wk of gestation (HFL22w) corresponds to the turning point between immigration and emigration of the hematopoietic system. To gain further molecular insight into its developmental and functi...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.175501

    authors: Yu Y,Zhang C,Zhou G,Wu S,Qu X,Wei H,Xing G,Dong C,Zhai Y,Wan J,Ouyang S,Li L,Zhang S,Zhou K,Zhang Y,Wu C,He F

    更新日期:2001-08-01 00:00:00

  • Active Alu element "A-tails": size does matter.

    abstract::Long and short interspersed elements (LINEs and SINEs) are retroelements that make up almost half of the human genome. L1 and Alu represent the most prolific human LINE and SINE families, respectively. Only a few Alu elements are able to retropose, and the factors determining their retroposition capacity are poorly un...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.384802

    authors: Roy-Engel AM,Salem AH,Oyeniran OO,Deininger L,Hedges DJ,Kilroy GE,Batzer MA,Deininger PL

    更新日期:2002-09-01 00:00:00

  • Pervasive, genome-wide positive selection leading to functional divergence in the bacterial genus Campylobacter.

    abstract::An open question in bacterial genomics is the role that adaptive evolution of the core genome plays in diversification and adaptation of bacterial species, and how this might differ between groups of bacteria occupying different environmental circumstances. The genus Campylobacter encompasses several important human a...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.089250.108

    authors: Lefébure T,Stanhope MJ

    更新日期:2009-07-01 00:00:00

  • Patterns of meiotic recombination on the long arm of human chromosome 21.

    abstract::In this study we quantify the features of meiotic recombination on the long arm of human chromosome 21. We constructed a 67. 3-centimorgan (cM) high-resolution, comprehensive, and accurate genetic linkage map of chromosome 21q using 187 highly polymorphic markers covering almost the entire long arm; 46 loci, consistin...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.138100

    authors: Lynn A,Kashuk C,Petersen MB,Bailey JA,Cox DR,Antonarakis SE,Chakravarti A

    更新日期:2000-09-01 00:00:00

  • A contiguous 66-kb barley DNA sequence provides evidence for reversible genome expansion.

    abstract::Organisms with large genomes contain vast amounts of repetitive DNA sequences, much of which is composed of retrotransposons. Amplification of retrotransposons has been postulated to be a major mechanism increasing genome size and leading to "genomic obesity." To gain insights into the relation between retrotransposon...

    journal_title:Genome research

    pub_type: 评论,杂志文章

    doi:10.1101/gr.10.7.908

    authors: Shirasu K,Schulman AH,Lahaye T,Schulze-Lefert P

    更新日期:2000-07-01 00:00:00

  • Multiparameter functional diversity of human C2H2 zinc finger proteins.

    abstract::C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.209643.116

    authors: Schmitges FW,Radovani E,Najafabadi HS,Barazandeh M,Campitelli LF,Yin Y,Jolma A,Zhong G,Guo H,Kanagalingam T,Dai WF,Taipale J,Emili A,Greenblatt JF,Hughes TR

    更新日期:2016-12-01 00:00:00

  • Genome-wide analyses of alternative splicing in plants: opportunities and challenges.

    abstract::Alternative splicing (AS) creates multiple mRNA transcripts from a single gene. While AS is known to contribute to gene regulation and proteome diversity in animals, the study of its importance in plants is in its early stages. However, recently available plant genome and transcript sequence data sets are enabling a g...

    journal_title:Genome research

    pub_type: 杂志文章,评审

    doi:10.1101/gr.053678.106

    authors: Barbazuk WB,Fu Y,McGinnis KM

    更新日期:2008-09-01 00:00:00

  • EbEST: an automated tool using expressed sequence tags to delineate gene structure.

    abstract::Large numbers of expressed sequence tags (ESTs) continue to fill public and private databases with partial cDNA sequences. However, using this huge amount of ESTs to facilitate gene finding in genomic sequence imposes a challenge, especially to wet-lab scientists who often have limited computing resources. In an effor...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.8.3.268

    authors: Jiang J,Jacob HJ

    更新日期:1998-03-01 00:00:00

  • Spidey: a tool for mRNA-to-genomic alignments.

    abstract::We have developed a computer program that aligns spliced sequences to genomic sequences, using local alignment algorithms and heuristics to put together a global spliced alignment. Spidey can produce reliable alignments quickly, even when confronted with noise from alternative splicing, polymorphisms, sequencing error...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.195301

    authors: Wheelan SJ,Church DM,Ostell JM

    更新日期:2001-11-01 00:00:00

  • Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.

    abstract::By analyzing 1,780,295 5'-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by m...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.4039406

    authors: Kimura K,Wakamatsu A,Suzuki Y,Ota T,Nishikawa T,Yamashita R,Yamamoto J,Sekine M,Tsuritani K,Wakaguri H,Ishii S,Sugiyama T,Saito K,Isono Y,Irie R,Kushida N,Yoneyama T,Otsuka R,Kanda K,Yokoi T,Kondo H,Wagatsuma M

    更新日期:2006-01-01 00:00:00

  • Comparing genomes within the species Mycobacterium tuberculosis.

    abstract::The study of genetic variability within natural populations of pathogens may provide insight into their evolution and pathogenesis. We used a Mycobacterium tuberculosis high-density oligonucleotide microarray to detect small-scale genomic deletions among 19 clinically and epidemiologically well-characterized isolates ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.166401

    authors: Kato-Maeda M,Rhee JT,Gingeras TR,Salamon H,Drenkow J,Smittipat N,Small PM

    更新日期:2001-04-01 00:00:00

  • Detecting copy number variation with mated short reads.

    abstract::The development of high-throughput sequencing (HTS) technologies has opened the door to novel methods for detecting copy number variants (CNVs) in the human genome. While in the past CNVs have been detected based on array CGH data, recent studies have shown that depth-of-coverage information from HTS technologies can ...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.106344.110

    authors: Medvedev P,Fiume M,Dzamba M,Smith T,Brudno M

    更新日期:2010-11-01 00:00:00

  • Gene loss and movement in the maize genome.

    abstract::Maize (Zea mays L. ssp. mays), one of the most important agricultural crops in the world, originated by hybridization of two closely related progenitors. To investigate the fate of its genes after tetraploidization, we analyzed the sequence of five duplicated regions from different chromosomal locations. We also compa...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.2701104

    authors: Lai J,Ma J,Swigonová Z,Ramakrishna W,Linton E,Llaca V,Tanyolac B,Park YJ,Jeong OY,Bennetzen JL,Messing J

    更新日期:2004-10-01 00:00:00

  • Construction of a linkage map of the medaka (Oryzias latipes) and mapping of the Da mutant locus defective in dorsoventral patterning.

    abstract::Double anal fin (Da) is a medaka with an autosomal semidominant mutation that causes mirror image duplication of the ventral region concentrating on the caudal region. The chromosomal location of the Da gene and its sequence have remained unknown. We constructed a medaka linkage map as a first step to approach positio...

    journal_title:Genome research

    pub_type: 杂志文章

    doi:10.1101/gr.9.12.1277

    authors: Ohtsuka M,Makino S,Yoda K,Wada H,Naruse K,Mitani H,Shima A,Ozato K,Kimura M,Inoko H

    更新日期:1999-12-01 00:00:00