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  • 1
    Publication Date: 2008-02-19
    Description: Cytosine DNA methylation is important in regulating gene expression and in silencing transposons and other repetitive sequences. Recent genomic studies in Arabidopsis thaliana have revealed that many endogenous genes are methylated either within their promoters or within their transcribed regions, and that gene methylation is highly correlated with transcription levels. However, plants have different types of methylation controlled by different genetic pathways, and detailed information on the methylation status of each cytosine in any given genome is lacking. To this end, we generated a map at single-base-pair resolution of methylated cytosines for Arabidopsis, by combining bisulphite treatment of genomic DNA with ultra-high-throughput sequencing using the Illumina 1G Genome Analyser and Solexa sequencing technology. This approach, termed BS-Seq, unlike previous microarray-based methods, allows one to sensitively measure cytosine methylation on a genome-wide scale within specific sequence contexts. Here we describe methylation on previously inaccessible components of the genome and analyse the DNA methylation sequence composition and distribution. We also describe the effect of various DNA methylation mutants on genome-wide methylation patterns, and demonstrate that our newly developed library construction and computational methods can be applied to large genomes such as that of mouse.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377394/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377394/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cokus, Shawn J -- Feng, Suhua -- Zhang, Xiaoyu -- Chen, Zugen -- Merriman, Barry -- Haudenschild, Christian D -- Pradhan, Sriharsa -- Nelson, Stanley F -- Pellegrini, Matteo -- Jacobsen, Steven E -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Mar 13;452(7184):215-9. doi: 10.1038/nature06745. Epub 2008 Feb 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18278030" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Animals ; Arabidopsis/*genetics ; Base Sequence ; Computational Biology ; Cytosine/metabolism ; *DNA Methylation ; Gene Expression Regulation, Plant/genetics ; Gene Library ; Genome, Plant/*genetics ; Mice ; Mutation/genetics ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Sequence Analysis, DNA/*methods ; Sulfites/*metabolism ; Uracil/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2004-12-25
    Description: A major focus of genome research is to decipher the networks of molecular interactions that underlie cellular function. We describe a computational approach for identifying detailed relationships between proteins on the basis of genomic data. Logic analysis of phylogenetic profiles identifies triplets of proteins whose presence or absence obey certain logic relationships. For example, protein C may be present in a genome only if proteins A and B are both present. The method reveals many previously unidentified higher order relationships. These relationships illustrate the complexities that arise in cellular networks because of branching and alternate pathways, and they also facilitate assignment of cellular functions to uncharacterized proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bowers, Peter M -- Cokus, Shawn J -- Eisenberg, David -- Yeates, Todd O -- New York, N.Y. -- Science. 2004 Dec 24;306(5705):2246-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15618515" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Physiological Phenomena ; Bacterial Proteins/*analysis/chemistry/*physiology ; *Computational Biology ; *Genome ; *Genome, Bacterial ; Logic ; Movement ; Phylogeny ; Protein Array Analysis ; *Protein Interaction Mapping ; Proteins/*analysis/genetics/*physiology ; Shikimic Acid/metabolism ; Virulence
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2010-06-01
    Description: Nucleosomes compact and regulate access to DNA in the nucleus, and are composed of approximately 147 bases of DNA wrapped around a histone octamer. Here we report a genome-wide nucleosome positioning analysis of Arabidopsis thaliana using massively parallel sequencing of mononucleosomes. By combining this data with profiles of DNA methylation at single base resolution, we identified 10-base periodicities in the DNA methylation status of nucleosome-bound DNA and found that nucleosomal DNA was more highly methylated than flanking DNA. These results indicate that nucleosome positioning influences DNA methylation patterning throughout the genome and that DNA methyltransferases preferentially target nucleosome-bound DNA. We also observed similar trends in human nucleosomal DNA, indicating that the relationships between nucleosomes and DNA methyltransferases are conserved. Finally, as has been observed in animals, nucleosomes were highly enriched on exons, and preferentially positioned at intron-exon and exon-intron boundaries. RNA polymerase II (Pol II) was also enriched on exons relative to introns, consistent with the hypothesis that nucleosome positioning regulates Pol II processivity. DNA methylation is also enriched on exons, consistent with the targeting of DNA methylation to nucleosomes, and suggesting a role for DNA methylation in exon definition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964354/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964354/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chodavarapu, Ramakrishna K -- Feng, Suhua -- Bernatavichute, Yana V -- Chen, Pao-Yang -- Stroud, Hume -- Yu, Yanchun -- Hetzel, Jonathan A -- Kuo, Frank -- Kim, Jin -- Cokus, Shawn J -- Casero, David -- Bernal, Maria -- Huijser, Peter -- Clark, Amander T -- Kramer, Ute -- Merchant, Sabeeha S -- Zhang, Xiaoyu -- Jacobsen, Steven E -- Pellegrini, Matteo -- GM07104/GM/NIGMS NIH HHS/ -- GM42143/GM/NIGMS NIH HHS/ -- GM60398/GM/NIGMS NIH HHS/ -- R37 GM042143/GM/NIGMS NIH HHS/ -- R37 GM060398/GM/NIGMS NIH HHS/ -- R37 GM060398-10/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jul 15;466(7304):388-92. doi: 10.1038/nature09147. Epub 2010 May 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20512117" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/enzymology/*genetics/*metabolism ; Chromatin Assembly and Disassembly/genetics/*physiology ; Chromatin Immunoprecipitation ; DNA Methylation/genetics/*physiology ; DNA Polymerase II/analysis/metabolism ; DNA, Plant/genetics/metabolism ; Exons/genetics ; Genes, Plant/genetics ; Genome, Plant/genetics ; Humans ; Micrococcal Nuclease/metabolism ; Nucleosomes/genetics/*metabolism ; Sequence Analysis, DNA
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2010-01-26
    Description: Epigenetic reprogramming including demethylation of DNA occurs in mammalian primordial germ cells (PGCs) and in early embryos, and is important for the erasure of imprints and epimutations, and the return to pluripotency. The extent of this reprogramming and its molecular mechanisms are poorly understood. We previously showed that the cytidine deaminases AID and APOBEC1 can deaminate 5-methylcytosine in vitro and in Escherichia coli, and in the mouse are expressed in tissues in which demethylation occurs. Here we profiled DNA methylation throughout the genome by unbiased bisulphite next generation sequencing in wild-type and AID-deficient mouse PGCs at embryonic day (E)13.5. Wild-type PGCs revealed marked genome-wide erasure of methylation to a level below that of methylation deficient (Np95(-/-), also called Uhrf1(-/-)) embryonic stem cells, with female PGCs being less methylated than male ones. By contrast, AID-deficient PGCs were up to three times more methylated than wild-type ones; this substantial difference occurred throughout the genome, with introns, intergenic regions and transposons being relatively more methylated than exons. Relative hypermethylation in AID-deficient PGCs was confirmed by analysis of individual loci in the genome. Our results reveal that erasure of DNA methylation in the germ line is a global process, hence limiting the potential for transgenerational epigenetic inheritance. AID deficiency interferes with genome-wide erasure of DNA methylation patterns, indicating that AID has a critical function in epigenetic reprogramming and potentially in restricting the inheritance of epimutations in mammals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965733/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965733/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Popp, Christian -- Dean, Wendy -- Feng, Suhua -- Cokus, Shawn J -- Andrews, Simon -- Pellegrini, Matteo -- Jacobsen, Steven E -- Reik, Wolf -- G0700098/Medical Research Council/United Kingdom -- R37 GM060398/GM/NIGMS NIH HHS/ -- R37 GM060398-11/GM/NIGMS NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Howard Hughes Medical Institute/ -- Medical Research Council/United Kingdom -- England -- Nature. 2010 Feb 25;463(7284):1101-5. doi: 10.1038/nature08829.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20098412" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cytidine Deaminase/*deficiency/genetics/*metabolism ; *DNA Methylation ; DNA Transposable Elements/genetics ; Embryo, Mammalian/cytology/embryology/metabolism ; Epigenesis, Genetic/genetics ; Exons/genetics ; Female ; *Genome/genetics ; Germ Cells/enzymology/*metabolism ; Introns/genetics ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins/deficiency/genetics ; Octamer Transcription Factor-3/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-05-05
    Description: Transposable elements (TEs) and DNA repeats are commonly targeted by DNA and histone methylation to achieve epigenetic gene silencing. We isolated mutations in two Arabidopsis genes, AtMORC1 and AtMORC6, which cause derepression of DNA-methylated genes and TEs but no losses of DNA or histone methylation. AtMORC1 and AtMORC6 are members of the conserved Microrchidia (MORC) adenosine triphosphatase (ATPase) family, which are predicted to catalyze alterations in chromosome superstructure. The atmorc1 and atmorc6 mutants show decondensation of pericentromeric heterochromatin, increased interaction of pericentromeric regions with the rest of the genome, and transcriptional defects that are largely restricted to loci residing in pericentromeric regions. Knockdown of the single MORC homolog in Caenorhabditis elegans also impairs transgene silencing. We propose that the MORC ATPases are conserved regulators of gene silencing in eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376212/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moissiard, Guillaume -- Cokus, Shawn J -- Cary, Joshua -- Feng, Suhua -- Billi, Allison C -- Stroud, Hume -- Husmann, Dylan -- Zhan, Ye -- Lajoie, Bryan R -- McCord, Rachel Patton -- Hale, Christopher J -- Feng, Wei -- Michaels, Scott D -- Frand, Alison R -- Pellegrini, Matteo -- Dekker, Job -- Kim, John K -- Jacobsen, Steven E -- F32 GM100617/GM/NIGMS NIH HHS/ -- F32GM100617/GM/NIGMS NIH HHS/ -- GM007185/GM/NIGMS NIH HHS/ -- GM075060/GM/NIGMS NIH HHS/ -- GM088565/GM/NIGMS NIH HHS/ -- GM60398/GM/NIGMS NIH HHS/ -- HG003143/HG/NHGRI NIH HHS/ -- R01 GM075060/GM/NIGMS NIH HHS/ -- R01 GM088565/GM/NIGMS NIH HHS/ -- R01 HG003143/HG/NHGRI NIH HHS/ -- R37 GM060398/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Jun 15;336(6087):1448-51. doi: 10.1126/science.1221472. Epub 2012 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, Terasaki Life Sciences Building, 610 Charles Young Drive East, Los Angeles, CA 90095-723905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22555433" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/chemistry/genetics/*metabolism ; Animals ; Arabidopsis/enzymology/*genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/genetics/metabolism ; Centromere ; DNA Methylation ; DNA Transposable Elements ; *Gene Silencing ; Genes, Plant ; Heterochromatin/*metabolism/ultrastructure ; Histones/metabolism ; Methylation ; Mutation ; RNA, Small Interfering/metabolism ; Transcription, Genetic ; Transgenes ; Up-Regulation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2012-05-03
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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