Heredity(2010)105,1-3 c 2010 Macmillan Publishers Limited All rights reserved 0018-067X/10 $32.00 www.nature.com/hdy EDITORIAL and epigenomics tell us? pe What do epigenetics From genotype to phenotyl Heredity2010)105,1-3;:doi:10.1038/hdy201066 (H3K9me3)by histone meth ylang ifferences within rase and heter chromatin protein 1. Epigenetic High-throughput sequencing is becoming quicker and natural populations and between various ecotypes have increasingly affordable, and as a result there has been a been linked to variation in DNA methylation (johannes et al., 2009)and even seem to be directed by small genomes have been sequenced. This is yielding large interfering Roas that match to specific geno mic regions amounts of genomic information that can be used to mammalian genomes have been found to be differen- tackle many questions in genetics and genomics from a tially methylated, with their methylated status depend comparative perspective: the structure and composition of genomes in relation to the environment, how specia ing on cis-acting factors(Schilling et aL., 2009), suggesting that they may influence the overall phenotype. Indeed, tion occurs, the processes of domestication, responses to has been clearly shown that deficiencies stress and so on. However, although classical genetic methylation are deleterious and usually lead to early analyses and the omic' technologies (transcriptomic, embryo mortality, and that any surviving unmethylated proteomic, metabolomic and so on) will continue to mutants exhibit developmental aberrations of progres- provide important information, new and unexpecte sive severity (Mathieu et al., 2007). This indicates that any information may also result from studying epigenetic mutation that leads to the misexpression of genes processes(DNa methylation, histone modifications, involved in epigenetic control will have a major effect RNA interference), which do not change the sequence throughout development and may even lead to the onset of the DNA itself, but modify the way genes are of diseases in adulthood, including some tumors expressed during development. Analyzing the large For epigenetics to have an important role in popul wide profiling of DNA methylation and histone mod- be handed down from parents to offspring, and so ifications)is a major challenge involving biologists, transmitted down the generations. In mammals, most comput epigenetic marks are erased betv tions, but because there is increasing evidence of differences in epigenetic reprogramming occurs early in embryogen epigenetic patterns between individuals (Lister et al, esis, and it is now clear that this erasure is incomplete Recent research into the contribution of epigenetics to the development and across generations is that of the differential regulation of gene expression, imprinting "imprinted genes'. The expression of these enes ending on the parent-of- pends on their parent-of-origin and they produce their origin), gene silencing and the involvement of transpo- effects during embryonic development or later on in sable elements (TEs) in these processes, have all shed development. The mechanisms involved in this imprint fresh light on the relationships between genotype and ing phenomenon and its evolution are reviewed by reviews that covers epigenetic processes occurring at by Koehler and Weinhofer-Molisch in plants The pano DNA methylation is an epigenetic mark that is often by specific regions known as imprinting control regions associated with histone modifications (methylation, (ICRs). These ICRs acquire their DNA methylation acetylation, phosphorylation and so on), chromatin pattern in the male germline, and the paternal imprint conformation and RNA interference, all of which are is protected against demethylation in the paternal processes that regulate gene transcription during em- genome of the zygote. The methylated imprint is thus bryonic and subsequent development. Gibney and Nolan maintained throughout development(Kacem and Feil, review the overall role of epigenetics in influencing gene 2009)in the somatic cell lineage. One important xpression during differentiation and development; characteristic of ICRs is that maternally methylated ICRs in all sequence contexts, whereas in animals it is mostly resembles the paramutations that have been reported in CGs that are methylated(Feng et al., 2010: Law and plants and in the mouse, in which the two parent-of Jacobsen, 2010); Dambacher, Hahn and Schotta present rigin alleles can influence each others expression cutting-edge research about the part played by histone These enetic modifications are also known to be lysine methylation in regulating development, and transmitted to the offspring. Misexpression of imprinted Rountree and Selker review the impact of dna genes has been shown to be associated with early methylation on the formation of heterochromatin in embryonic lethality and post-natal development in Neurospora crassa, revealing the close interrelationships mammals, and has recently also been identified in plants that exist between the methylation of histone H3 lysine 9(Bayer et al., 2009). Around 100 imprinted genesEDITORIAL From genotype to phenotype. What do epigenetics and epigenomics tell us? Heredity (2010) 105, 1–3; doi:10.1038/hdy.2010.66 High-throughput sequencing is becoming quicker and increasingly affordable, and as a result there has been a dramatic increase in the number of species of which the genomes have been sequenced. This is yielding large amounts of genomic information that can be used to tackle many questions in genetics and genomics from a comparative perspective: the structure and composition of genomes in relation to the environment, how specia￾tion occurs, the processes of domestication, responses to stress and so on. However, although classical genetic analyses and the ‘omic’ technologies (transcriptomic, proteomic, metabolomic and so on) will continue to provide important information, new and unexpected information may also result from studying epigenetic processes (DNA methylation, histone modifications, RNA interference), which do not change the sequence of the DNA itself, but modify the way genes are expressed during development. Analyzing the large amount of data available about epigenomes (genome￾wide profiling of DNA methylation and histone mod￾ifications) is a major challenge involving biologists, bioinformatics specialists and computer biologists, because there is increasing evidence of differences in epigenetic patterns between individuals (Lister et al., 2009), and even between different tissues and cell types. Recent research into the contribution of epigenetics to the differential regulation of gene expression, imprinting (differential gene expression depending on the parent-of￾origin), gene silencing and the involvement of transpo￾sable elements (TEs) in these processes, have all shed fresh light on the relationships between genotype and phenotype. In this special issue, we provide a selection of reviews that covers epigenetic processes occurring at several different levels and in various organisms. DNA methylation is an epigenetic mark that is often associated with histone modifications (methylation, acetylation, phosphorylation and so on), chromatin conformation and RNA interference, all of which are processes that regulate gene transcription during em￾bryonic and subsequent development. Gibney and Nolan review the overall role of epigenetics in influencing gene expression during differentiation and development; Teixeira and Colot then summarize the effects of DNA methylation in plants, in which cytosines are methylated in all sequence contexts, whereas in animals it is mostly CGs that are methylated (Feng et al., 2010; Law and Jacobsen, 2010); Dambacher, Hahn and Schotta present cutting-edge research about the part played by histone lysine methylation in regulating development, and Rountree and Selker review the impact of DNA methylation on the formation of heterochromatin in Neurospora crassa, revealing the close interrelationships that exist between the methylation of histone H3 lysine 9 (H3K9me3) by histone methyltransferase and hetero￾chromatin protein 1. Epigenetic differences within natural populations and between various ecotypes have been linked to variation in DNA methylation (Johannes et al., 2009) and even seem to be directed by small interfering RNAs that match to specific genomic regions (Zhai et al., 2008). Several hundred regions of the DNA of mammalian genomes have been found to be differen￾tially methylated, with their methylated status depend￾ing on cis-acting factors (Schilling et al., 2009), suggesting that they may influence the overall phenotype. Indeed, it has been clearly shown that deficiencies in DNA methylation are deleterious and usually lead to early embryo mortality, and that any surviving unmethylated mutants exhibit developmental aberrations of progres￾sive severity (Mathieu et al., 2007). This indicates that any mutation that leads to the misexpression of genes involved in epigenetic control will have a major effect throughout development and may even lead to the onset of diseases in adulthood, including some tumors. For epigenetics to have an important role in popula￾tions, epigenetic marks and epigenetic alterations need to be handed down from parents to offspring, and so transmitted down the generations. In mammals, most epigenetic marks are erased between generations, but epigenetic reprogramming occurs early in embryogen￾esis, and it is now clear that this erasure is incomplete. A good example of epigenetic transmission during development and across generations is that of the ‘imprinted genes’. The expression of these genes de￾pends on their parent-of-origin and they produce their effects during embryonic development or later on in development. The mechanisms involved in this imprint￾ing phenomenon and its evolution are reviewed by Hudson, Kulinski, Huetter and Barlow in the mouse and by Koehler and Weinhofer-Molisch in plants. The parent￾of-origin expression of the imprinting genes is regulated by specific regions known as imprinting control regions (ICRs). These ICRs acquire their DNA methylation pattern in the male germline, and the paternal imprint is protected against demethylation in the paternal genome of the zygote. The methylated imprint is thus maintained throughout development (Kacem and Feil, 2009) in the somatic cell lineage. One important characteristic of ICRs is that maternally methylated ICRs can exert promoter activity on the paternal allele and sometimes silence it. This kind of interallelic talk resembles the paramutations that have been reported in plants and in the mouse, in which the two parent-of￾origin alleles can influence each other’s expression. These epigenetic modifications are also known to be transmitted to the offspring. Misexpression of imprinted genes has been shown to be associated with early embryonic lethality and post-natal development in mammals, and has recently also been identified in plants (Bayer et al., 2009). Around 100 imprinted genes Heredity (2010) 105, 1–3 & 2010 Macmillan Publishers Limited All rights reserved 0018-067X/10 $32.00 www.nature.com/hdy