Non-methylated islands in fish genomes are GC-poor.
Ontology highlight
ABSTRACT:
SUBMITTER: Cross S
PROVIDER: S-EPMC333903 | biostudies-other | 1991 Apr
REPOSITORIES: biostudies-other
Publications
Non-methylated islands in fish genomes are GC-poor.
Cross S S Kovarik P P Schmidtke J J Bird A A
Nucleic acids research 19910401 7
In the vertebrate genomes studied to date the 5' end of many genes are associated with distinctive sequences known as CpG islands. CpG islands have three properties: they are non-methylated; the dinucleotide CpG occurs at the frequency predicted by base composition; and they are GC-rich. Unexpectedly we have found that CpG islands in certain fish only have the first two properties; that is, their GC-content is not elevated compared to bulk genomic DNA. Based on this finding, we speculate that th ...[more]
Similar Datasets
Project description:Non-methylated islands (NMIs) of DNA are genomic regions that are important for gene regulation and development. A recent study of genome-wide non-methylation data in vertebrates by Long et al. (eLife 2013;2:e00348) has shown that many experimentally identified non-methylated regions do not overlap with classically defined CpG islands which are computationally predicted using simple DNA sequence features. This is especially true in cold-blooded vertebrates such as Danio rerio (zebrafish). In order to investigate how predictive DNA sequence is of a region's methylation status, we applied a supervised learning approach using a spectrum kernel support vector machine, to see if a more complex model and supervised learning can be used to improve non-methylated island prediction and to understand the sequence properties of these regions. We demonstrate that DNA sequence is highly predictive of methylation status, and that in contrast to existing CpG island prediction methods our method is able to provide more useful predictions of NMIs genome-wide in all vertebrate organisms that were studied. Our results also show that in cold-blooded vertebrates (Anolis carolinensis, Xenopus tropicalis and Danio rerio) where genome-wide classical CpG island predictions consist primarily of false positives, longer primarily AT-rich DNA sequence features are able to identify these regions much more accurately.
| S-EPMC5161304 | biostudies-literature
Project description:BackgroundTeleost fish genome size has been repeatedly demonstrated to positively correlate with the proportion of transposable elements (TEs). This finding might have far-reaching implications for our understanding of the evolution of nucleotide composition across vertebrates. Genomes of fish and amphibians are GC homogenous, with non-teleost gars being the single exception identified to date, whereas birds and mammals are AT/GC heterogeneous. The exact reason for this phenomenon remains controversial. Since TEs make up significant proportions of genomes and can quickly accumulate across genomes, they can potentially influence the host genome with their own GC content (GC%). However, the GC% of fish TEs has so far been neglected.ResultsThe genomic proportion of TEs indeed correlates with genome size, although not as linearly as previously shown with fewer genomes, and GC% negatively correlates with genome size in the 33 fish genome assemblies analysed here (excluding salmonids). GC% of fish TE consensus sequences positively correlates with the corresponding genomic GC% in 29 species tested. Likewise, the GC contents of the entire repetitive vs. non-repetitive genomic fractions correlate positively in 54 fish species in Ensembl. However, among these fish species, there is also a wide variation in GC% between the main groups of TEs. Class II DNA transposons, predominant TEs in fish genomes, are significantly GC-poorer than Class I retrotransposons. The AT/GC heterogeneous gar genome contains fewer Class II TEs, a situation similar to fugu with its extremely compact and also GC-enriched but AT/GC homogenous genome.ConclusionOur results reveal a previously overlooked correlation between GC% of fish genomes and their TEs. This applies to both TE consensus sequences as well as the entire repetitive genomic fraction. On the other hand, there is a wide variation in GC% across fish TE groups. These results raise the question whether GC% of TEs evolves independently of GC% of the host genome or whether it is driven by TE localization in the host genome. Answering these questions will help to understand how genomic GC% is shaped over time. Long-term accumulation of GC-poor(er) Class II DNA transposons might indeed have influenced AT/GC homogenization of fish genomes and requires further investigation.
| S-EPMC6909575 | biostudies-literature
Project description:BackgroundParasitoid wasps have fascinating life cycles and play an important role in trophic networks, yet little is known about their genome content and function. Parasitoids that infect aphids are an important group with the potential for biological control. Their success depends on adapting to develop inside aphids and overcoming both host aphid defenses and their protective endosymbionts.ResultsWe present the de novo genome assemblies, detailed annotation, and comparative analysis of two closely related parasitoid wasps that target pest aphids: Aphidius ervi and Lysiphlebus fabarum (Hymenoptera: Braconidae: Aphidiinae). The genomes are small (139 and 141 Mbp) and the most AT-rich reported thus far for any arthropod (GC content: 25.8 and 23.8%). This nucleotide bias is accompanied by skewed codon usage and is stronger in genes with adult-biased expression. AT-richness may be the consequence of reduced genome size, a near absence of DNA methylation, and energy efficiency. We identify missing desaturase genes, whose absence may underlie mimicry in the cuticular hydrocarbon profile of L. fabarum. We highlight key gene groups including those underlying venom composition, chemosensory perception, and sex determination, as well as potential losses in immune pathway genes.ConclusionsThese findings are of fundamental interest for insect evolution and biological control applications. They provide a strong foundation for further functional studies into coevolution between parasitoids and their hosts. Both genomes are available at https://bipaa.genouest.org.
| S-EPMC7257214 | biostudies-literature
Project description:CFP1 is a CXXC domain-containing protein and an essential component of the SETD1 histone H3K4 methyltransferase complex. CXXC domain proteins direct different chromatin-modifying activities to various chromatin regions. Here, we report crystal structures of the CFP1 CXXC domain in complex with six different CpG DNA sequences. The crescent-shaped CFP1 CXXC domain is wedged into the major groove of the CpG DNA, distorting the B-form DNA, and interacts extensively with the major groove of the DNA. The structures elucidate the molecular mechanism of the non-methylated CpG-binding specificity of the CFP1 CXXC domain. The CpG motif is confined by a tripeptide located in a rigid loop, which only allows the accommodation of the non-methylated CpG dinucleotide. Furthermore, we demonstrate that CFP1 has a preference for a guanosine nucleotide following the CpG motif.
| S-EPMC3072069 | biostudies-literature
Project description:Densely methylated DNA sequence islands, designated DMIs, have been observed in two Chinese hamster cell chromosomal replication origins by using a PCR-based chemical method of detection. One of the origins, oriS14, is located within or adjacent to the coding sequence for ribosomal protein S14 on chromosome 2q, and the other, ori-beta, is approximately 17 kbp downstream of the dhfr (dihydrofolic acid reductase) locus on chromosome 2p. The DMI in oriS14 is 127 bp long, and the DMI in ori-beta is 516 bp long. Both DMIs are bilaterally methylated (i.e., all dCs are modified to 5-methyl dC) only in cells that are replicating their DNA. When cell growth and DNA replication are arrested, methylation of CpA, CpT, and CpC dinucleotides is lost and the sequence islands display only a subset of their originally methylated CpG dinucleotides. Several possible roles for DMI-mediated regulation of mammalian chromosomal origins are considered.
| S-EPMC359088 | biostudies-other
Project description:Metagenomic sequencing is a well-established tool in the modern biosciences. While it promises unparalleled insights into the genetic content of the biological samples studied, conclusions drawn are at risk from biases inherent to the DNA sequencing methods, including inaccurate abundance estimates as a function of genomic guanine-cytosine (GC) contents. We explored such GC biases across many commonly used platforms in experiments sequencing multiple genomes (with mean GC contents ranging from 28.9% to 62.4%) and metagenomes. GC bias profiles varied among different library preparation protocols and sequencing platforms. We found that our workflows using MiSeq and NextSeq were hindered by major GC biases, with problems becoming increasingly severe outside the 45-65% GC range, leading to a falsely low coverage in GC-rich and especially GC-poor sequences, where genomic windows with 30% GC content had >10-fold less coverage than windows close to 50% GC content. We also showed that GC content correlates tightly with coverage biases. The PacBio and HiSeq platforms also evidenced similar profiles of GC biases to each other, which were distinct from those seen in the MiSeq and NextSeq workflows. The Oxford Nanopore workflow was not afflicted by GC bias. These findings indicate potential sources of difficulty, arising from GC biases, in genome sequencing that could be pre-emptively addressed with methodological optimizations provided that the GC biases inherent to the relevant workflow are understood. Furthermore, it is recommended that a more critical approach be taken in quantitative abundance estimates in metagenomic studies. In the future, metagenomic studies should take steps to account for the effects of GC bias before drawing conclusions, or they should use a demonstrably unbiased workflow.
| S-EPMC7016772 | biostudies-literature
Project description:BackgroundMammalian CpG islands (CGIs) normally escape DNA methylation in all adult tissues and developmental stages. However, in our previous study we unexpectedly identified many methylated CGIs in human peripheral blood leukocytes. Methylated CpG dinucleotides convert to TpG dinucleotides through deaminization of their cytosine bases more frequently than hypomethylated CpG dinucleotides. Therefore, we wondered how methylated CGIs in germline or non-germline cells maintain their CpG-rich sequences. It is known that events such as germline hypomethylation, CpG selection, biased gene conversion (BGC), and frequent CpG fixation can contribute to the maintenance of CpG-rich sequences in methylated CGIs in germline or non-germline cells. However, it has not been investigated which of the processes maintain CpG-rich sequences of methylated CGIs in each genomic position.ResultsIn this study, we comprehensively examined the contribution of the processes described above to the maintenance of CpG-rich sequences in methylated CGIs in germline and non-germline cells which were classified by genomic positions. Approximately 60-80% of CGIs with high methylation in H1 cell line (H1-HM) in all the genomic positions showed a low average CpG→TpG/CpA substitution rate. In contrast, fewer than half the numbers of CGIs with H1-HM in all the genomic positions showed a low average CpG→TpG/CpA substitution rate and low levels of methylation in sperm cells (SPM-LM). Furthermore, a small fraction of CGIs with a low average CpG→TpG/CpA substitution rate and high levels of methylation in sperm cells (SPM-HM) showed CpG selection. On the other hand, independent of the positions in genes, most CGIs with SPM-HM showed a slightly higher average TpG/CpA→CpG substitution rate compared with those with SPM-LM.ConclusionsRelatively high numbers (approximately 60-80%) of CGIs with H1-HM in all the genomic positions preserve their CpG-rich sequences by a low CpG→TpG/CpA substitution rate caused mainly by their SPM-LM, and for those with SPM-HM partly by CpG selection and TpG/CpA→CpG fixation. BGC has little contribution to the maintenance of CpG-rich sequences of CGIs with SPM-HM which were classified by genomic positions.
| S-EPMC4417305 | biostudies-literature
Project description:Hypermethylation of promoter CpG islands is strongly correlated to transcriptional gene silencing and epigenetic maintenance of the silenced state. As well as its role in tumor development, CpG island methylation contributes to the acquisition of resistance to chemotherapy. Differential Methylation Hybridisation (DMH) is one technique used for genome-wide DNA methylation analysis. The study of such microarray data sets should ideally account for the specific biological features of DNA methylation and the non-symmetrical distribution of the ratios of unmethylated and methylated sequences hybridised on the array. We have therefore developed a novel algorithm tailored to this type of data, Methylation Linear Discriminant Analysis (MLDA).MLDA was programmed in R (version 2.7.0) and the package is available at CRAN 1. This approach utilizes linear regression models of non-normalised hybridisation data to define methylation status. Log-transformed signal intensities of unmethylated controls on the microarray are used as a reference. The signal intensities of DNA samples digested with methylation sensitive restriction enzymes and mock digested are then transformed to the likelihood of a locus being methylated using this reference. We tested the ability of MLDA to identify loci differentially methylated as analysed by DMH between cisplatin sensitive and resistant ovarian cancer cell lines. MLDA identified 115 differentially methylated loci and 23 out of 26 of these loci have been independently validated by Methylation Specific PCR and/or bisulphite pyrosequencing.MLDA has advantages for analyzing methylation data from CpG island microarrays, since there is a clear rational for the definition of methylation status, it uses DMH data without between-group normalisation and is less influenced by cross-hybridisation of loci. The MLDA algorithm successfully identified differentially methylated loci between two classes of samples analysed by DMH using CpG island microarrays.
| S-EPMC2529322 | biostudies-literature
Project description:Identifying cis-regulatory regions in mammalian genomes is a key challenge toward understanding transcriptional regulation. However, identification and functional characterization of those regulatory elements governing differential gene expression has been hampered by the limited understanding of their organization and locations in genomes. We hypothesized that genes that are conserved across species will also display conservation at the level of their transcriptional regulation and that this will be reflected in the organization of cis-elements mediating this regulation. Using a computational approach, clusters of transcription factor binding sites that are absolutely conserved in order and in spacing across human, rat, and mouse genomes were identified. We term these regions pattern-defined regulatory islands (PRIs). We discovered that these sequences are frequently active sites of transcriptional regulation. These PRIs occur in approximately 1.1% of the half-billion base pairs covered in the search and are located mainly in noncoding regions of the genome. We show that the premise of PRIs can be used to identify previously known and novel cis-regulatory regions controlling genes regulated by myogenic differentiation. Thus, PRIs may represent a fundamental property of the architecture of cis-regulatory elements in mammalian genomes, and this feature can be exploited to pinpoint critical transcriptional regulatory elements governing cell type-specific gene expression.
| S-EPMC1891267 | biostudies-literature
Project description:In every kingdom of life, GC->AT transitions occur more frequently than any other type of mutation due to the spontaneous deamination of cytidine. In eukaryotic genomes, this slow loss of GC base pairs is counteracted by biased gene conversion which increases genomic GC content as part of the recombination process. However, this type of biased gene conversion has not been observed in bacterial genomes, so we hypothesized that GC->AT transitions cause a reduction of genomic GC content in prokaryotic genomes on an evolutionary time scale. To test this hypothesis, we used a phylogenetic approach to analyze triplets of closely related genomes representing a wide range of the bacterial kingdom. The resulting data indicate that genomic GC content is drifting downward in bacterial genomes where GC base pairs comprise 40% or more of the total genome. In contrast, genomes containing less than 40% GC base pairs have fewer opportunities for GC->AT transitions to occur so genomic GC content is relatively stable or actually increasing. It should be noted that this observed change in genomic GC content is the net change in shared parts of the genome and does not apply to parts of the genome that have been lost or acquired since the genomes being compared shared common ancestor. However, a more detailed analysis of two Caulobacter genomes revealed that the acquisition of mobile elements by the two genomes actually reduced the total genomic GC content as well.
| S-EPMC8153448 | biostudies-literature