The function of intragenic DNA methylation: insights from insect epigenomes.

Epigenetic inheritance plays a fundamentally important role in mediating gene regulation and phenotypic plasticity. DNA methylation, in particular, has been the focus of many recent studies aimed at understanding the function of epigenetic information in insects. An understanding of DNA methylation, however, requires knowledge of its context in relation to other epigenetic modifications. Here, we review recent insights into the localization of DNA methylation in insect genomes and further discuss the functional significance of these insights in the context of the greater eukaryotic epigenome. In particular, we highlight the complementarity of the eukaryotic epigenetic landscape. We focus on the importance of DNA methylation to nucleosome stability, which may explain the context-dependent associations of DNA methylation with gene expression. Ultimately, we suggest that the integration of diverse epigenetic modifications in studies of insects will greatly advance our understanding of the evolution of epigenetic systems and epigenetic contributions to developmental regulation.

[1]  Allen D. Delaney,et al.  Conserved Role of Intragenic DNA Methylation in Regulating Alternative Promoters , 2010, Nature.

[2]  R. F. Luco,et al.  Epigenetics in Alternative Pre-mRNA Splicing , 2011, Cell.

[3]  R. Kucharski,et al.  DNA methylation changes elicited by social stimuli in the brains of worker honey bees , 2012, Genes, brain, and behavior.

[4]  C. Bustamante,et al.  Nucleosomal Elements that Control the Topography of the Barrier to Transcription , 2012, Cell.

[5]  Joel Dudley,et al.  TimeTree: a public knowledge-base of divergence times among organisms , 2006, Bioinform..

[6]  Taesung Park,et al.  Comparative analyses of DNA methylation and sequence evolution using Nasonia genomes. , 2011, Molecular biology and evolution.

[7]  Soojin V Yi,et al.  Birds do it, bees do it, worms and ciliates do it too: DNA methylation from unexpected corners of the tree of life , 2012, Genome Biology.

[8]  J. Ahringer,et al.  Differential chromatin marking of introns and expressed exons by H3K36me3 , 2008, Nature Genetics.

[9]  M. Goodisman,et al.  Functional Conservation of DNA Methylation in the Pea Aphid and the Honeybee , 2010, Genome biology and evolution.

[10]  Pierre-Étienne Jacques,et al.  The Euchromatic and Heterochromatic Landscapes Are Shaped by Antagonizing Effects of Transcription on H2A.Z Deposition , 2009, PLoS genetics.

[11]  M. Snyder,et al.  A High-Resolution Whole-Genome Map of Key Chromatin Modifications in the Adult Drosophila melanogaster , 2011, PLoS genetics.

[12]  F. Ratnieks,et al.  Comparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA methylation and CpG landscapes in other invertebrates. , 2011, Genome research.

[13]  S. Forêt,et al.  The Honey Bee Epigenomes: Differential Methylation of Brain DNA in Queens and Workers , 2010, PLoS biology.

[14]  Jan Komorowski,et al.  Nucleosomes are well positioned in exons and carry characteristic histone modifications. , 2009, Genome research.

[15]  S. Pennings,et al.  DNA methylation, nucleosome formation and positioning. , 2005, Briefings in functional genomics & proteomics.

[16]  D. Schübeler,et al.  Determinants and dynamics of genome accessibility , 2011, Nature Reviews Genetics.

[17]  S. Jacobsen,et al.  Epigenetic modifications in plants: an evolutionary perspective. , 2011, Current opinion in plant biology.

[18]  Nicole I Bieberstein,et al.  First exon length controls active chromatin signatures and transcription. , 2012, Cell reports.

[19]  J. Bell,et al.  A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues , 2011, PLoS genetics.

[20]  M. Gerstein,et al.  Unlocking the secrets of the genome , 2009, Nature.

[21]  S. Henikoff,et al.  Histone H2A.Z and DNA methylation are mutually antagonistic chromatin marks , 2008, Nature.

[22]  P. Jones,et al.  The DNA methylation paradox. , 1999, Trends in genetics : TIG.

[23]  Eric S. Lander,et al.  Genomic Maps and Comparative Analysis of Histone Modifications in Human and Mouse , 2005, Cell.

[24]  R. F. Luco,et al.  More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation. , 2011, Current opinion in genetics & development.

[25]  Soojin V. Yi,et al.  DNA Methylation and Genome Evolution in Honeybee: Gene Length, Expression, Functional Enrichment Covary with the Evolutionary Signature of DNA Methylation , 2010, Genome biology and evolution.

[26]  Danny Reinberg,et al.  A chromatin link to caste identity in the carpenter ant Camponotus floridanus , 2013, Genome research.

[27]  Lovelace J. Luquette,et al.  Comprehensive analysis of the chromatin landscape in Drosophila , 2010, Nature.

[28]  S. Henikoff,et al.  Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription , 2007, Nature Genetics.

[29]  April N. Allen,et al.  Genome-wide association between DNA methylation and alternative splicing in an invertebrate , 2012, BMC Genomics.

[30]  Wen-Hsiung Li,et al.  Coordinated histone modifications are associated with gene expression variation within and between species. , 2011, Genome research.

[31]  A. Bird,et al.  Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals , 2003, Nature Genetics.

[32]  Guillaume J. Filion,et al.  Systematic Protein Location Mapping Reveals Five Principal Chromatin Types in Drosophila Cells , 2010, Cell.

[33]  Danny Reinberg,et al.  Molecular Signals of Epigenetic States , 2010, Science.

[34]  M. Pellegrini,et al.  Relationship between nucleosome positioning and DNA methylation , 2010, Nature.

[35]  Y. Pittelkow,et al.  Epigenetic regulation of the honey bee transcriptome: unravelling the nature of methylated genes , 2009, BMC Genomics.

[36]  B. Bernstein,et al.  Charting histone modifications and the functional organization of mammalian genomes , 2011, Nature Reviews Genetics.

[37]  S. Henikoff,et al.  Genome-scale profiling of histone H3.3 replacement patterns , 2005, Nature Genetics.

[38]  Hui Xiang,et al.  Genome-wide and Caste-Specific DNA Methylomes of the Ants Camponotus floridanus and Harpegnathos saltator , 2012, Current Biology.

[39]  Peter A. Jones Functions of DNA methylation: islands, start sites, gene bodies and beyond , 2012, Nature Reviews Genetics.

[40]  S. Henikoff,et al.  Genome-Wide Kinetics of Nucleosome Turnover Determined by Metabolic Labeling of Histones , 2010, Science.

[41]  B. Hunt,et al.  The evolution of invertebrate gene body methylation. , 2012, Molecular biology and evolution.

[42]  John T. Lis,et al.  Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans , 2012, Nature Reviews Genetics.

[43]  M. Goodisman,et al.  Evidence of a conserved functional role for DNA methylation in termites , 2013, Insect molecular biology.

[44]  M. Goodisman,et al.  DNA methylation in insects: on the brink of the epigenomic era , 2011, Insect molecular biology.

[45]  J. Sedat,et al.  The absence of detectable methylated bases in Drosophila melanogaster DNA , 1982, FEBS letters.

[46]  A. Kornblihtt,et al.  A slow RNA polymerase II affects alternative splicing in vivo. , 2003, Molecular cell.

[47]  V. Studitsky,et al.  RNA polymerase complexes cooperate to relieve the nucleosomal barrier and evict histones , 2010, Proceedings of the National Academy of Sciences.

[48]  S. Henikoff,et al.  Changes in H2A.Z occupancy and DNA methylation during B-cell lymphomagenesis. , 2010, Genome research.

[49]  Steven Chu,et al.  DNA methylation increases nucleosome compaction and rigidity. , 2010, Journal of the American Chemical Society.

[50]  J. Workman,et al.  Signals and combinatorial functions of histone modifications. , 2011, Annual review of biochemistry.

[51]  Amy L. Toth,et al.  Epigenetics in Social Insects: A New Direction for Understanding the Evolution of Castes , 2012, Genetics research international.

[52]  Ju Yeon Lee,et al.  Effects of DNA methylation on the structure of nucleosomes. , 2012, Journal of the American Chemical Society.

[53]  D. Coleman-Derr,et al.  Deposition of Histone Variant H2A.Z within Gene Bodies Regulates Responsive Genes , 2012, PLoS genetics.

[54]  A. Kornblihtt,et al.  Promoter usage and alternative splicing. , 2005, Current opinion in cell biology.

[55]  M. Pellegrini,et al.  Conservation and divergence of methylation patterning in plants and animals , 2010, Proceedings of the National Academy of Sciences.

[56]  J. Lieb,et al.  Control of Transcription through Intragenic Patterns of Nucleosome Composition , 2005, Cell.

[57]  D. Geschwind,et al.  Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution. , 2012, American journal of human genetics.

[58]  Wen-Hsiung Li,et al.  Evolutionary conservation of histone modifications in mammals. , 2012, Molecular biology and evolution.

[59]  V. Studitsky,et al.  Histone N-terminal Tails Interfere with Nucleosome Traversal by RNA Polymerase II* , 2008, Journal of Biological Chemistry.

[60]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[61]  R. Sandberg,et al.  CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing , 2011, Nature.

[62]  Matthew T. Maurano,et al.  Widespread plasticity in CTCF occupancy linked to DNA methylation , 2012, Genome research.

[63]  A. Bird,et al.  Genomic DNA methylation: the mark and its mediators. , 2006, Trends in biochemical sciences.

[64]  M. Goodisman,et al.  Patterning and Regulatory Associations of DNA Methylation Are Mirrored by Histone Modifications in Insects , 2013, Genome biology and evolution.

[65]  Andrew P. Feinberg,et al.  Reversible switching between epigenetic states in honeybee behavioral subcastes , 2012, Nature Neuroscience.

[66]  A. Bird,et al.  DNA methylation landscapes: provocative insights from epigenomics , 2008, Nature Reviews Genetics.

[67]  K. Kristiansen,et al.  Single base–resolution methylome of the silkworm reveals a sparse epigenomic map , 2010, Nature Biotechnology.

[68]  Steven Henikoff,et al.  Histone variants — ancient wrap artists of the epigenome , 2010, Nature Reviews Molecular Cell Biology.

[69]  Steven Henikoff,et al.  Nucleosome destabilization in the epigenetic regulation of gene expression , 2008, Nature Reviews Genetics.

[70]  Gos Micklem,et al.  Supporting Online Material Materials and Methods Figs. S1 to S50 Tables S1 to S18 References Identification of Functional Elements and Regulatory Circuits by Drosophila Modencode , 2022 .

[71]  Felix Krueger,et al.  Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications , 2011, Bioinform..

[72]  M. Goodisman,et al.  DNA methylation is widespread and associated with differential gene expression in castes of the honeybee, Apis mellifera , 2009, Proceedings of the National Academy of Sciences.

[73]  G. Ast,et al.  Chromatin organization marks exon-intron structure , 2009, Nature Structural &Molecular Biology.

[74]  Bing Li,et al.  Histone H3 Methylation by Set2 Directs Deacetylation of Coding Regions by Rpd3S to Suppress Spurious Intragenic Transcription , 2005, Cell.

[75]  Steven Henikoff,et al.  Histone modification: cause or cog? , 2011, Trends in genetics : TIG.

[76]  W. Reik,et al.  Shifting behaviour: epigenetic reprogramming in eusocial insects. , 2012, Current opinion in cell biology.

[77]  A. Bird DNA methylation patterns and epigenetic memory. , 2002, Genes & development.

[78]  I. King Jordan,et al.  On the presence and role of human gene-body DNA methylation , 2012, Oncotarget.

[79]  A. Moczek,et al.  DNA methylation as a mechanism of nutritional plasticity: limited support from horned beetles. , 2013, Journal of experimental zoology. Part B, Molecular and developmental evolution.

[80]  R. Kucharski,et al.  Nutritional Control of Reproductive Status in Honeybees via DNA Methylation , 2008, Science.

[81]  Robert L. Grossman,et al.  A cis-regulatory map of the Drosophila genome , 2011, Nature.

[82]  B. Blencowe,et al.  Regulation of Alternative Splicing by Histone Modifications , 2010, Science.

[83]  G. Robinson,et al.  DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees , 2012, Proceedings of the National Academy of Sciences.

[84]  D. Zilberman,et al.  Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation , 2010, Science.

[85]  Stefano Piccolo,et al.  MicroRNA control of signal transduction , 2010, Nature Reviews Molecular Cell Biology.

[86]  Eric Vigoda,et al.  Mutations of Different Molecular Origins Exhibit Contrasting Patterns of Regional Substitution Rate Variation , 2008, PLoS Comput. Biol..

[87]  H. Cedar,et al.  Linking DNA methylation and histone modification: patterns and paradigms , 2009, Nature Reviews Genetics.

[88]  A. Wolffe,et al.  How does DNA methylation repress transcription? , 1997, Trends in genetics : TIG.

[89]  Christoforos Nikolaou,et al.  Nucleosome positioning as a determinant of exon recognition , 2009, Nature Structural &Molecular Biology.

[90]  Christopher D. Smith,et al.  Patterns of DNA Methylation in Development, Division of Labor and Hybridization in an Ant with Genetic Caste Determination , 2012, PloS one.

[91]  Mark Groudine,et al.  Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells , 2004, Nature Structural &Molecular Biology.