Abstract:
BACKGROUND:The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferating cells such as colon tumours and the gut crypt progenitors, from which tumours can arise. RESULTS:Here, we show that colorectal tumours and cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. CONCLUSIONS:Together our results indicate that promoters that acquire 5hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC in tumours. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.
journal_name
Genome Bioljournal_title
Genome biologyauthors
Uribe-Lewis S,Stark R,Carroll T,Dunning MJ,Bachman M,Ito Y,Stojic L,Halim S,Vowler SL,Lynch AG,Delatte B,de Bony EJ,Colin L,Defrance M,Krueger F,Silva AL,Ten Hoopen R,Ibrahim AE,Fuks F,Murrell Adoi
10.1186/s13059-015-0605-5subject
Has Abstractpub_date
2015-04-01 00:00:00pages
69eissn
1474-7596issn
1474-760Xpii
s13059-015-0605-5journal_volume
16pub_type
杂志文章相关文献
GENOME BIOLOGY文献大全abstract:BACKGROUND:The influence of genetic variation on complex diseases is potentially mediated through a range of highly dynamic epigenetic processes exhibiting temporal variation during development and later life. Here we present a catalogue of the genetic influences on DNA methylation (methylation quantitative trait loci ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-016-0926-z
更新日期:2016-03-31 00:00:00
abstract:BACKGROUND:Single-cell transcriptomics is rapidly advancing our understanding of the cellular composition of complex tissues and organisms. A major limitation in most analysis pipelines is the reliance on manual annotations to determine cell identities, which are time-consuming and irreproducible. The exponential growt...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-019-1795-z
更新日期:2019-09-09 00:00:00
abstract:BACKGROUND:The nature of the protein molecular clock, the protein-specific rate of amino acid substitutions, is among the central questions of molecular evolution. Protein expression level is the dominant determinant of the clock rate in a number of organisms. It has been suggested that highly expressed proteins evolve...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2010-11-9-r98
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Epigenomic studies that use next generation sequencing experiments typically rely on the alignment of reads to a reference sequence. However, because of genetic diversity and the diploid nature of the human genome, we hypothesize that using a generic reference could lead to incorrectly mapped reads and bias ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-020-02038-8
更新日期:2020-05-25 00:00:00
abstract:BACKGROUND:Abundant pseudogenes are a feature of mammalian genomes. Processed pseudogenes (PPs) are reverse transcribed from mRNAs. Recent molecular biological studies show that mammalian long interspersed element 1 (L1)-encoded proteins may have been involved in PP reverse transcription. Here, we present the first com...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2003-4-11-r74
更新日期:2003-01-01 00:00:00
abstract::Two recent studies demonstrate the power of integrating tumor genotype information with epigenetic and proteomic studies to discover potential therapeutic targets in breast cancer. ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-017-1238-7
更新日期:2017-05-22 00:00:00
abstract:BACKGROUND:The newly assembled Bos taurus genome sequence enables the linkage of bovine milk and lactation data with other mammalian genomes. RESULTS:Using publicly available milk proteome data and mammary expressed sequence tags, 197 milk protein genes and over 6,000 mammary genes were identified in the bovine genome...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2009-10-4-r43
更新日期:2009-01-01 00:00:00
abstract::A report on the Epigenetic Engineering Meeting hosted by the Barts Institute of Cancer, held in London, UK, May 7, 2014. ...
journal_title:Genome biology
pub_type:
doi:10.1186/gb4179
更新日期:2014-01-01 00:00:00
abstract::A report of the Wellcome Trust Functional Genomics and Systems Biology Conference, Hinxton, UK, 29 November to 1 December 2011. ...
journal_title:Genome biology
pub_type:
doi:10.1186/gb-2012-13-1-312
更新日期:2012-01-30 00:00:00
abstract::Compared to RNA-sequencing transcript differential analysis, gene-level differential expression analysis is more robust and experimentally actionable. However, the use of gene counts for statistical analysis can mask transcript-level dynamics. We demonstrate that 'analysis first, aggregation second,' where the p value...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-018-1419-z
更新日期:2018-04-12 00:00:00
abstract::From worms to humans, recognizing and modifying a specific chromosome is essential for dosage compensation, the mechanism by which equal X-linked gene expression in males and females is achieved. Recent molecular genetic and biochemical studies have provided new insights into how regulatory factors in Drosophila are r...
journal_title:Genome biology
pub_type: 杂志文章,评审
doi:10.1186/gb-2000-1-6-reviews1030
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND:Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in hu...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2006-7-10-r95
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Mutations in genes encoding ribosomal proteins (RPs) have been shown to cause an array of cellular and developmental defects in a variety of organisms. In Drosophila melanogaster, disruption of RP genes can result in the 'Minute' syndrome of dominant, haploinsufficient phenotypes, which include prolonged dev...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2007-8-10-r216
更新日期:2007-01-01 00:00:00
abstract::Droplet-based single-cell RNA sequencing protocols have dramatically increased the throughput of single-cell transcriptomics studies. A key computational challenge when processing these data is to distinguish libraries for real cells from empty droplets. Here, we describe a new statistical method for calling cells fro...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-019-1662-y
更新日期:2019-03-22 00:00:00
abstract::Microarray analysis using clustering algorithms can suffer from lack of inter-method consistency in assigning related gene-expression profiles to clusters. Obtaining a consensus set of clusters from a number of clustering methods should improve confidence in gene-expression analysis. Here we introduce consensus cluste...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2004-5-11-r94
更新日期:2004-01-01 00:00:00
abstract::Levels of transcripts sharing microRNA response elements are co-regulated. These RNA-RNA interactions imply that combinations of microRNAs modulate cell-specific transcript networks. ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2011-12-11-132
更新日期:2011-11-21 00:00:00
abstract::A recent study reveals a surprisingly high degree of change in the occupancy patterns of two transcription factors in the livers of five vertebrates. ...
journal_title:Genome biology
pub_type: 评论,杂志文章
doi:10.1186/gb-2010-11-6-122
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Whole genome sequencing of marine cyanobacteria has revealed an unprecedented degree of genomic variation and streamlining. With a size of 1.66 megabase-pairs, Prochlorococcus sp. MED4 has the most compact of these genomes and it is enigmatic how the few identified regulatory proteins efficiently sustain the...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2005-6-9-r73
更新日期:2005-01-01 00:00:00
abstract::We have developed an ontology to provide standardized nomenclature for anatomical terms in the postnatal mouse. The Adult Mouse Anatomical Dictionary is structured as a directed acyclic graph, and is organized hierarchically both spatially and functionally. The ontology will be used to annotate and integrate different...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2005-6-3-r29
更新日期:2005-01-01 00:00:00
abstract::Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmark vg against...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-020-1941-7
更新日期:2020-02-12 00:00:00
abstract::Most microbes cannot be easily cultured, and metagenomics provides a means to study them. Current techniques aim to resolve individual genomes from metagenomes, so-called metagenome-assembled genomes (MAGs). Leading approaches depend upon time series or transect studies, the efficacy of which is a function of communit...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-019-1643-1
更新日期:2019-02-26 00:00:00
abstract::DNA arrays are valuable tools in molecular biology laboratories. Their rapid acceptance was aided by the release of plans for a pin-spotting microarrayer by researchers at Stanford. Inkjet microarraying is a flexible, complementary technique that allows the synthesis of arrays of any oligonucleotide sequences de novo....
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2004-5-8-r58
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Evolutionary centromere repositioning and human analphoid neocentromeres occurring in clinical cases are, very likely, two stages of the same phenomenon whose properties still remain substantially obscure. Chromosome 13 is the chromosome with the highest number of neocentromeres. We reconstructed the mammali...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2006-7-10-r91
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:ADAR proteins are among the most extensively studied RNA binding proteins. They bind to their target and deaminate specific adenosines to inosines. ADAR activity is essential, and the editing of a subset of their targets is critical for viability. Recently, a huge number of novel ADAR targets were detected b...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2014-15-1-r5
更新日期:2014-01-07 00:00:00
abstract:BACKGROUND:Pre-mRNA splicing is an essential step in gene expression that occurs co-transcriptionally in the cell nucleus, involving a large number of RNA binding protein splicing factors, in addition to core spliceosome components. Several of these proteins are required for the recognition of intronic sequence element...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2006-7-11-r113
更新日期:2006-01-01 00:00:00
abstract::We present a new method, Fine-Mapping of Adaptive Variation (FineMAV), which combines population differentiation, derived allele frequency, and molecular functionality to prioritize positively selected candidate variants for functional follow-up. We calibrate and test FineMAV using eight experimentally validated "gold...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-017-1380-2
更新日期:2018-01-17 00:00:00
abstract:BACKGROUND:There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challe...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2014-15-3-r53
更新日期:2014-03-25 00:00:00
abstract::Droplet-based microfluidic devices have become widely used to perform single-cell RNA sequencing (scRNA-seq). However, ambient RNA present in the cell suspension can be aberrantly counted along with a cell's native mRNA and result in cross-contamination of transcripts between different cell populations. DecontX is a n...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-020-1950-6
更新日期:2020-03-05 00:00:00
abstract::We used scaled factorial moments to search for intermittency in the log expression ratios (LERs) for thousands of genes spotted on cDNA microarrays (gene chips). Results indicate varying levels of intermittency in gene expression. The observation of intermittency in the data analyzed provides a complimentary handle on...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2002-3-7-preprint0005
更新日期:2002-05-29 00:00:00
abstract::Transcription factor binding sites compete for a limited pool of bioavailable transcription factor molecules to fine tune gene expression. ...
journal_title:Genome biology
pub_type: 评论,杂志文章
doi:10.1186/gb4174
更新日期:2014-04-28 00:00:00