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203
A bivalent chromatin structure marks key developmental genes in embryonic stem cells, Cell 125
, 2006
"... The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by ex ..."
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The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed ‘‘bivalent domains,’ ’ consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.
An evaluation of new criteria for CpG islands in the human genome as gene markers
- Bioinformatics
, 2004
"... Motivation: Recently, more stringent criteria for CpG islands have been introduced to exclude Alu repeats, thereby enabling a higher proportion of CpG islands associating with genes to be identified. Using these new criteria, several types of associations between CpG islands and genes were investiga ..."
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Cited by 24 (0 self)
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Motivation: Recently, more stringent criteria for CpG islands have been introduced to exclude Alu repeats, thereby enabling a higher proportion of CpG islands associating with genes to be identified. Using these new criteria, several types of associations between CpG islands and genes were investigated to further establish the importance of CpG islands as gene markers. Results: The CpG islands were searched by CpGIE, a java software program developed for CpG island identification. CpGIE was advanced in identification accuracy compared with other tools. According to our results, about 70 % of the identified CpG islands were associating with the human genes and over half of them are in the promoters. Furthermore, the investigation of genes in the confirmed gene model showed that 56 % of them had a CpG island overlapping the transcription start sites. In comparison, the new criteria were found capable of filtering a large fraction of Alu repeats that was identified as CpG islands by the generally accepted criteria within the genes, but very few CpG islands associating with the promoters were affected. The genes in the predicted gene model were not obviously associated with CpG islands, suggesting that CpG islands can be used to evaluate the accuracy of gene annotation.
CpGcluster: A distance-based algorithm for CpG-island detection,
- BMC Bioinformatics,
, 2006
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doi:10.1093/nar/gki987 Analysis of repetitive element DNA methylation
, 2005
"... Repetitive elements represent a large portion of the human genome and contain much of the CpG methylation found in normal human postnatal somatic tissues. Loss of DNA methylation in these sequences might account for most of the global hypomethylation that characterizes a large percentage of human ca ..."
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Cited by 24 (4 self)
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Repetitive elements represent a large portion of the human genome and contain much of the CpG methylation found in normal human postnatal somatic tissues. Loss of DNA methylation in these sequences might account for most of the global hypomethylation that characterizes a large percentage of human cancers that have been studied. There is widespread interest in correlating the genomic 5-methylcytosine content with clinical outcome, dietary history, lifestyle, etc. However, a high-throughput, accurate and easily accessible technique that can be applied even to paraffin-embedded tissue DNA is not yet available. Here, we report the development of quantitative MethyLight assays to determine the
CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome. Nucleic Acids Res 33:2952–2961
, 2005
"... ABSTRACT An effective tool for the global analysis of both DNA methylation status and protein-chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type of array suited for this purpose takes advantage of the strong association between CpG Islands (CG ..."
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Cited by 23 (5 self)
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ABSTRACT An effective tool for the global analysis of both DNA methylation status and protein-chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type of array suited for this purpose takes advantage of the strong association between CpG Islands (CGIs) and gene regulatory regions. We have obtained 20 736 clones from a CGI Library and used these to construct CGI arrays. The utility of this library requires proper annotation and assessment of the clones, including CpG content, genomic origin and proximity to neighboring genes. Alignment of clone sequences to the human genome (UCSC hg17) identified 9595 distinct genomic loci; 64% were defined by a single clone while the remaining 36% were represented by multiple, redundant clones. Approximately 68% of the loci were located near a transcription start site. The distribution of these loci covered all 23 chromosomes, with 63% overlapping a bioinformatically identified CGI. The high representation of genomic CGI in this rich collection of clones supports the utilization of microarrays produced with this library for the study of global epigenetic mechanisms and proteinchromatin interactions. A browsable database is available on-line to facilitate exploration of the CGIs in this library and their association with annotated genes or promoter elements.
CpG islands - ‘a rough guide
- FEBS Lett
"... a b s t r a c t Mammalian genomes are punctuated by DNA sequences containing an atypically high frequency of CpG sites termed CpG islands (CGIs). CGIs generally lack DNA methylation and associate with the majority of annotated gene promoters. Many studies, however, have identified examples of CGI m ..."
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Cited by 20 (0 self)
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a b s t r a c t Mammalian genomes are punctuated by DNA sequences containing an atypically high frequency of CpG sites termed CpG islands (CGIs). CGIs generally lack DNA methylation and associate with the majority of annotated gene promoters. Many studies, however, have identified examples of CGI methylation in malignant cells, leading to improper gene silencing. CGI methylation also occurs in normal tissues and is known to function in X-inactivation and genomic imprinting. More recently, differential methylation has been shown between tissues, suggesting a potential role in transcriptional regulation during cell specification. Many of these tissue-specific methylated CGIs localise to regions distal to promoters, the regulatory function of which remains to be determined.
DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter
- Hum. Mol. Genet
, 2011
"... g.oxfordjournals.org/ D ow nloaded from 2 Despite the fact that 45 % of all human gene promoters do not contain CpG islands, the role of DNA methylation in control of non-CpG island promoters is controversial and its relevance in normal and pathological processes is poorly understood. Among the few ..."
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Cited by 19 (0 self)
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g.oxfordjournals.org/ D ow nloaded from 2 Despite the fact that 45 % of all human gene promoters do not contain CpG islands, the role of DNA methylation in control of non-CpG island promoters is controversial and its relevance in normal and pathological processes is poorly understood. Among the few studies which investigate the correlation between DNA methylation and expression of genes with non-CpG island promoters, the majority do not support the view that DNA methylation directly leads to transcription silencing of these genes. Our reporter assays and gene reactivation by 5-aza-2’-deoxycytidine, a DNA demethylating agent, show that DNA methylation occurring at CpG poor LAMB3 promoter and RUNX3 promoter 1(RUNX3 P1) can directly lead to transcriptional silencing in cells competent to express these genes in vitro. Using Nucleosome Occupancy
Large-scale structural analysis of the core promoter in mammalian and plant genomes: Nucl
- Acids Res
, 2005
"... mammalian and plant genomes ..."
Chromatin structure and evolution in the human genome.
- BMC Evol. Biol.
, 2007
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K.-M.: Locating non-overlapping maximum average segments in a given sequence
- Bioinformatics
, 2003
"... Summary: MAVG is a software tool for finding k non-overlapping maximum-average segments that are sufficiently long in a given sequence of real numbers, for any k> 0. It has applications in several areas of biomolec-ular sequence analysis including locating GC-rich regions and CpG islands in a gen ..."
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Cited by 13 (5 self)
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Summary: MAVG is a software tool for finding k non-overlapping maximum-average segments that are sufficiently long in a given sequence of real numbers, for any k> 0. It has applications in several areas of biomolec-ular sequence analysis including locating GC-rich regions and CpG islands in a genomic sequence, and annotating multiple sequence alignments.