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G Model YSCDB-800; No. of Pages 6 ARTICLE IN PRESS Seminars in Cell & Developmental Biology xxx (2008) xxx–xxx Contents lists available at ScienceDirect Seminars in Cell & Developmental Biology journal homepage: www.elsevier.com/locate/semcdb Review Genomic imprinting: A balance between antagonistic roles of parental chromosomes Tetsu Kinoshita ∗ , Yoko Ikeda, Ryo Ishikawa Plant Reproductive Genetics, GCOE Research Group, Graduate School of Biological Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan a r t i c l e Article history: Available online xxx Keywords: Genomic imprinting Endosperm Reproductive barrier Apomixis i n f o a b s t r a c t Maternally and paternally derived chromosomes might be expected to contribute equally to the various cellular and developmental processes in placental mammals and flowering plants. However, this is not true even in the case of the self-pollinated plant, Arabidopsis, which has identical DNA sequences in both parental genomes. The reason for this is that some genes, called “imprinted genes”, are expressed exclusively from paternally or maternally inherited chromosomes. As a result, parental chromosomes express a distinct set of genes and play different roles in biological processes. Here, we review and compare roles of genomic imprinting in flowering plants and placental mammals. © 2008 Elsevier Ltd. All rights reserved. Contents 1. 2. 3. 4. 5. 6. 7. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Control of imprinted genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DNA methylation cycle of imprinted genes in mammals and one-way control of imprinted genes by DNA methylation in flowering plants . . . . Mechanism of DNA demethylation of imprinted genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Role of genomic imprinting in parthenogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Role of genomic imprinting in reproductive barriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Introduction Genomic imprinting refers to the unequal expression of maternal and paternal alleles of a gene depending on the parent-of-origin, and is a phenomenon that has evolved in both placental mammals and flowering plants. In both mammals and plants, the imprinted genes are differentially marked before fertilization by DNA methylation and histone modifications [1]. As a consequence of the heritable epigenetic marks on the imprinted genes, the roles of maternally and paternally inherited chromosomes are not equivalent in cellular and developmental processes. These epigenetic modifications have been used to explain functional differences between parental genomes. In mammals, gynogenetic or androgenetic embryos, which have two sets of maternal or paternal ∗ Corresponding author. Tel.: +81 743 72 6210; fax: +81 743 72 6210. E-mail address: [email protected] (T. Kinoshita). 00 00 00 00 00 00 00 00 00 chromosomes, respectively, show opposite effects on the development of the placenta; they also display many developmental abnormalities and do not develop beyond the mid-gestation stage [2,3]. In flowering plants, an increased dosage of maternal chromosomes usually promotes endosperm development, while an increased dosage of paternal chromosomes represses endosperm development [4,5]. Both the placenta and the endosperm are tissues that provide nutrients to the embryo [6]. One proposed explanation of the evolution of imprinting, the parental conflict theory, predicts that maternally expressed imprinted genes reduce nutritional flow to the embryo, while paternally expressed imprinted genes promote nutritional flow [7]. In this review, we focus on the mechanism of genomic imprinting in flowering plants in comparison to that of placental mammals. Recent studies of Arabidopsis mutants have identified several imprinted genes [8–12]. Although the life histories of mammals and plants are very different, the imprinting of genes in plants are controlled by DNA methylation and histone modification(s) as is 1084-9521/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.semcdb.2008.07.018 Please cite this article in press as: Kinoshita T, et al. Genomic imprinting: A balance between antagonistic roles of parental chromosomes. Semin Cell Dev Biol (2008), doi:10.1016/j.semcdb.2008.07.018 G Model YSCDB-800; No. of Pages 6 2 ARTICLE IN PRESS T. Kinoshita et al. / Seminars in Cell & Developmental Biology xxx (2008) xxx–xxx the case for mammalian genomic imprinting. We also extend our consideration of genomic imprinting in plants to discussion of its possible roles in various biological processes. As a consequence of the nature of epigenetic regulation of parental chromosomes, a balance between parental contributions has been predicted to play significant roles in endosperm development, reproductive barriers and apomixis [7]. 2. Control of imprinted genes In mammals, imprinted genes show a parent-of-origin specific gene expression pattern that relies on differential DNA methylation of the imprinting control regions (ICRs). Deletion of the ICR located upstream of the imprinted non-coding RNA gene, H19, results in loss of imprinted gene expression of Igf2 and H19 [13]. Although a variety of molecular mechanisms controlling genomic imprinting have been identified in mammals, such as chromatin looping, enhancer blocking, antisense transcripts and small RNAs [14–16], ICRs are the primary determinants of imprinted gene expression. Many maternally and paternally expressed imprinted genes are located in clusters near ICRs. In flowering plants, clusters of imprinted genes have not been identified, however, the epigenetic control of imprinted genes by DNA methylation and histone modifications are conserved [8,10,17–21]. In Arabidopsis, paternally inherited alleles of FWA and FIS2 are silenced by DNA methylation, while maternally inherited alleles are activated by the DNA glycosylase, DEMETER (DME) [8,20] (Fig. 1). A different layer of control of imprinted gene expression has also been reported [18,19,21]: the paternal allele of MEA is silenced by the histone methyltransferase activity of maternal MEA, which forms the evolutionarily conserved PRC2 Polycomb complex [22,23] (Fig. 1). This type of self-imprinting, in which a gene is silenced by its own product, is to date limited to plants, although the Polycomb complex is known to play a role in silencing of imprinted genes in the mammalian placenta [24]. Thus, DNA methylation and repression by the Polycomb complex are conserved aspects of genomic imprinting in placental mammals and flowering plants. Many transgenic constructs display an imprinted pattern of gene expression in Arabidopsis and maize suggesting that in plants the cis-element for controlling imprinted gene expression is most likely located near the imprinted loci [11,20,25–27]. In Arabidopsis, methylated DNA sequences have been found in the promoter regions of the maternally expressed imprinted genes MEDEA (MEA), FERTILIZATION-INDEPENDENT-SEED2 (FIS2) and FWA, and in the 3 -tandem repeats of the paternally expressed imprinted gene PHERES1 (PHE1). These methylated sequences are included in the transgenic constructs and, therefore, might confer imprinted gene expression. A well-studied example of a cis-element that controls genomic imprinting in plants is the SINE (short interspersed transposable element)-related tandem repeat structure located in the 5 -region of FWA [28–31]. The methylation status of the tandem repeats are always correlated with the expression pattern of FWA [28,32]. When methylation is lost, transcription starts within this repeat region and causes delayed flowering [32,33]. A transgene carrying the SINE-related tandem repeats with a GFP reporter construct showed a similar pattern of imprinted gene expression to the endogenous FWA gene [28]. Induced methylation of the hypomethylated allele of FWA, using an RNA-directed de novo DNA methylation strategy, showed that DNA methylation of SINE-related tandem repeats determine imprinted gene expression. An analysis of the evolution of this SINE-related tandem repeat, the region corresponding to this cis-element for imprinting in Arabidopsis species, has been reported [34]. This study suggested that a SINE-related sequence, without a tandem repeat structure, is responsible for the imprinted pattern of FWA expression in A. halleri [34]. Thus, in A. halleri at least, the tandem repeat structure, but not the SINE-related sequence, is dispensable for imprinting. The relationship between genomic imprinting and transposon insertion is of interest because in mammals the paternally expressed imprinted gene, PEG10, shows similarity to the sushi-ichi retrotransposon. PEG10 is only found in eutherian mammals, and is not present in non-mammalian vertebrates that have not evolved a placenta and genomic imprinting [35]. Due to the absence of evidence on imprinted gene clusters in flowering plants, it is not yet clear whether a long-distance control of genomic imprinting occurs. However, a recent report showed that the DNA methylation status of a 3 -tandem repeat about 2.5 kb downstream from the PHE1 locus affected the imprinted expression of the gene [25]. PHE1 encodes a MADS-box transcription factor and, in Arabidopsis, is a paternally expressed imprinted gene [9]. It was originally identified as a target gene of the polycomb group protein, MEA [36]. The 3 -tandem repeat of PHE1 is usually methylated in leaf tissue of wild type plants. However, in methyltransferase1 (met1) mutants, DNA methylation of the 3 -tandem repeat is lost and expression of the paternal allele is down-regulated. Furthermore, a transgene lacking the 3 -tandem repeat region did not display imprinted expression of PHE1. Thus, DNA methylation of the repeat is required for active expression of the paternal PHE1 allele. The authors proposed a hypothesis that DNA methylation of the 3 -tandem repeat of the maternal allele is erased by DME, which encodes a DNA glycosylase [18,25]. If this issue were proved, the epigenetic status of all known imprinted genes in Arabidopsis might be controlled in the central cell within the female gametophyte by DME. Although the underlying molecular mechanism is still not clear, the maternal control of imprinted genes in Arabidopsis is reminiscent of the control mechanism of mammalian imprinted genes. Despite the fact that the number of maternally and paternally expressed imprinted genes is almost equal in mammals, many of the methylation imprints of ICRs are marked during female gametogenesis. Only three loci, H19/Igf2, Rasgrf1/A19 and Dlk1/Gtl2, are known to be methylated in male gametogenesis [37]. 3. DNA methylation cycle of imprinted genes in mammals and one-way control of imprinted genes by DNA methylation in flowering plants As the life histories of placental mammals and flowering plants are very different, it is interesting to understand and compare how these different groups of organisms control the epigenetic status of their parental genomes. In mammals, the germ line is set aside during early embryogenesis [38], whereas in plants, male and female gametophytes form within the floral organs at late stages of development [39,40]. In addition to this difference in life history, genomic imprinting is restricted to the endosperm tissue of flowering plants, while imprinted genes are found in both the placenta and somatic tissues of mammals [6]. During evolution, placental mammals developed a strategy for the reprogramming of DNA methylation for genomic imprinting in each generation [41] (Fig. 2). In the primordial germ cells, the DNA methylation imprints marked in the previous generation are erased by an unknown, but presumably active, mechanism [42], and de novo DNA methylation imprints are established during gametogenesis. During gametogenesis, the de novo DNA methyltransferase, DNMT3A, and DNMT3L, which lacks conserved catalytic domain of methyltransferase, play a crucial role in the establishment of genomic imprinting [43–45]. DNMT3A and Please cite this article in press as: Kinoshita T, et al. Genomic imprinting: A balance between antagonistic roles of parental chromosomes. Semin Cell Dev Biol (2008), doi:10.1016/j.semcdb.2008.07.018 G Model YSCDB-800; No. of Pages 6 ARTICLE IN PRESS T. Kinoshita et al. / Seminars in Cell & Developmental Biology xxx (2008) xxx–xxx 3 Fig. 1. Control of imprinted genes in Arabidopsis. DNA methylation (asterisks) of imprinted genes, FWA, FIS2 and MEA, is erased by DME in the central cell. In contrast, the paternal alleles of these maternally expressed imprinted genes retain methylation in the male gametophyte. In the paternally expressed imprinted gene of PHE1, DNA methylation of the 3 -tandem repeat ensure active expression of the paternal allele, while the maternal allele of PHE1 is silenced by the polycomb complex in the central cell. After fertilization, the maternally derived alleles of FWA and FIS2 are expressed, while the paternally derived alleles are silenced by DNA methylation. The polycomb complex represses the paternally derived MEA and maternally derived PHE1 in the endosperm. The depicted outline omits fertilization of the egg cell and embryo as no evidence of genomic imprinting has yet been found in these tissues. DNMT3L knock-out mice show disrupted patterns of imprinted gene expression [43–45]. In contrast, in Arabidopsis, the plant homologue of the de novo methyltransferase gene, DOMAINREARRANGED-METHYLTRANSFERASE (DRM), has been reported to be dispensable for genomic imprinting [28,46]. If DNA methylation was erased and re-established in each generation in plants, then a de novo methyltransferase would be essential for this purpose. Analysis of DNA methylation patterns on the imprinted genes MEA and FWA in Arabidopsis and ZmFie1 in maize have revealed a distinct mechanism involving a “one-way” activation of the maternally transmitted allele of these genes [17,18,20,26,27] (Fig. 2). For maternally expressed imprinted genes, DNA demethylation of the 5 -promoter region is only observed in the central cell and endosperm, while paternal alleles retain DNA methylation in endosperm. In vegetative tissues, both maternal and paternal alleles retain their methylation pattern. Maintenance of methylation pattern is dependent on METHYLTRANSFERASE1 (MET1), the Arabidopsis homologue of DNMT1. Thus, DNA methylation appears to be a common epigenetic modification for controlling genomic imprinting in both plants and mammals, however, the mechanisms that regulate DNA methylation show distinct differences that reflect the different developmental patterns. Moreover, as the endosperm is a terminally differentiated tissue and does not transmit genetic or epigenetic information to the next generation, epigenetic reprogramming is not necessary in this plant tissue. 4. Mechanism of DNA demethylation of imprinted genes DNA demethylation is predicted to have a significant role in the epigenetic programming of imprinted genes in placental mammals and flowering plants. In mammals, methylation imprints are erased in the primordial germ cells (see above) although the molecular mechanism is still unclear and controversial. In Arabidopsis, the epigenetic programming of the maternally expressed imprinted genes, MEA, FWA and FIS2, is established in the central cell of the female gametophyte by the activity of the DNA glycosylase, DME [8,18,20,26]. DME is a large molecule containing an H1 linker histone domain and a conserved DNA glycosylase domain, similar to those in a base excision DNA repair protein, and can excise 5 -methylcytosine in vitro [18]. It is therefore likely that the base excision DNA repair machinery is involved in the demethylation of imprinted genes. The first step of base excision repair is removal of a base by DNA glycosylase; this is followed by cleavage of the abasic site by an AP lyase. The resulting nucleotide gap is filled by a DNA polymerase and completed by DNA ligase [47]. Although DME can catalyze the first two steps of base excision repair, i.e. can act as a so-called bifunctional DNA glycosylase [18], it is still unclear whether the enzymes for base excision repair in the remaining steps are involved in DNA demethylation. In the Xenopus oocyte, it has been shown that Gadd45a (Growth arrest and DNA damage inducible) can act synergistically with the repair endonuclease, XPG, to demethylate Oct4 [48]. Thus, a Please cite this article in press as: Kinoshita T, et al. Genomic imprinting: A balance between antagonistic roles of parental chromosomes. Semin Cell Dev Biol (2008), doi:10.1016/j.semcdb.2008.07.018 G Model YSCDB-800; 4 No. of Pages 6 ARTICLE IN PRESS T. Kinoshita et al. / Seminars in Cell & Developmental Biology xxx (2008) xxx–xxx Fig. 2. Patterns of DNA methylation of imprinted genes in placental mammals and flowering plants. In mammals, the pattern of DNA methylation marked in the previous generation (asterisks) is erased in PGCs (primordial germ cells). During gametogenesis, allele specific de novo methylation establishes genomic imprinting. Thus, the DNA methylation imprints on chromosomes are erased and established in each generation. In plants, the epigenetic asymmetry of parental chromosomes that is essential for genomic imprinting is only observed in the endosperm. Establishment of genomic imprinting occurs in the central cell by demethylation of methylated imprinted genes (see text). In contrast, the DNA methylation status of the paternal allele in the male gametophyte and endosperm, and those of the both alleles in vegetative tissues remains unchanged. functioning DNA demethylation mechanism through the base excision DNA repair pathway might be conserved in many organisms. In mammals, MBD4, which contains a methyl cytosine binding domain and a DNA glycosylase domain, has been implicated in DNA demethylation via the GT mismatch repair pathway [49]. Deamination of 5-methylcytosine induces a mismatched uracil that may be recognized by MBD4 or the GT mismatch repair enzyme. Interestingly, the 5-methylcytosine deaminase genes, Aid and Apobec1, are located in a cluster of pluripotency genes, including Nanog and PGC7/Stella, and co-expressed with these genes in the oocyte, the cell type in which genome-wide demethylation is observed [50]. 5. Role of genomic imprinting in parthenogenesis Parthenogenesis, the development of an unfertilized gamete into an embryo, is usually blocked by genetic mechanisms in placental mammals and flowering plants. One such mechanism was predicted from the results of nuclear transplantation experiments [2,3,7]. Formation of gynogenetic and androgenetic embryos by nuclear transplantation showed that the embryos displayed opposite phenotypes during development, especially in the placenta [2,3]. The most likely explanation for this opposite phenotype was that the maternally and paternally inherited genomes played different roles during embryonic development due to differences in epigenetic modification, such as genomic imprinting. Therefore, successful reproduction requires both maternal and paternal genomes, which enables the respective parental imprints to complement one another. This predicted role of genomic imprinting in parthenogenetic development was confirmed by the birth of a parthenogenetic mouse, KAGUYA [51,52]. KAGUYA had two sets of chromosomes of maternal origin. One chromosome set had been genetically manipulated with a large deletion of the differentially methylated domain and H19 so that the downstream enhancers could activate Igf2 expression. Thus, although KAGUYA has bi-maternal chromosome sets, epigenetic status of one of the chromosomes sets mimics that of paternally derived chromosomes and allows completion of embryonic development and birth. In flowering plants, genomic imprinting has been suggested to be a means to prevent asexual reproduction by allowing only successful seed production after fertilization of parental genomes that have complementary imprinted genes [7]. Since genomic imprinting is restricted to the endosperm tissue of flowering plants, sexual reproduction is essential to the parental genomes at least in the endosperm. Indeed, many apomictic species are psuedogamous: although the embryo develops from an unfertilized egg cell, the endosperm requires fertilization by the paternal genome [7]. In Arabidopsis, a combination of mutants of imprinted genes and CDKA;1, a homologue of Cdc2, demonstrated the role of genomic imprinting in preventing asexual development [53]. In the cdka;1 mutant, a cell cycle defect occurs in the second round of pollen mitosis and results in the formation of a single sperm pollen. This single sperm pollen preferentially fertilizes the egg cell and therefore the central cell is left unfertilized. The embryo develops after a single fertilization event, instead of the double fertilization that usually occurs in normal plant reproduction, but aborts at an early stage of embryo Please cite this article in press as: Kinoshita T, et al. Genomic imprinting: A balance between antagonistic roles of parental chromosomes. Semin Cell Dev Biol (2008), doi:10.1016/j.semcdb.2008.07.018 G Model YSCDB-800; No. of Pages 6 ARTICLE IN PRESS T. Kinoshita et al. / Seminars in Cell & Developmental Biology xxx (2008) xxx–xxx development with only a few rounds of proliferation of the central cell [54]. Strikingly, a combination of cdc2a and mea, fis2 or fie, which are mutants of the FIS-class complex and show autonomous endosperm development without fertilization [55,56], overcomes the seed lethality of the single fertilization described above. One interpretation is that the maternally expressed imprinted gene counterbalances the action of the paternal genome. Therefore, deletion of the maternally expressed imprinted gene allows seed development without a paternal contribution to the endosperm, which is related to the predicted role of genomic imprinting to apomixes. 6. Role of genomic imprinting in reproductive barriers As described above, a balance between the maternal and paternal contributions, repression and promotion of nutritional flow to the embryo, is required for post-zygotic development. This idea may also be applicable to the reproductive barrier between species in placental mammals and flowering plants. In mammals, inter-specific crosses between Peromyscus manicuatus (BW) and Peromyscus polionotus (PO) can produce viable progeny, although miscarriage of embryos is frequently observed when PO females are used [57]. When BW females are mated to PO males, abnormal placentas, approximately half-size of the parental species, and growth-retarded embryos are produced; the reciprocal cross results in overgrowth of placentas. This parent-of-origin dependent phenotype in inter-species breeding and the observed phenotype of loss-of-function of imprinted genes in mouse might explain the molecular basis of the post-zygotic reproductive barrier between these rodent species. In the hybrid Peromyscus mice, expression of many imprinted genes and X-linked loci are mis-regulated [57]. A backcross of the hybrid to the PO parental strain demonstrated a correlation between Peg3 expression, a paternally expressed imprinted gene, and placental weight [58]. This correlation is not conserved in Mus hybrids, however, suggesting that the underlying molecular mechanisms for the post-zygotic barrier vary [59]. Nevertheless, the mechanism of genomic imprinting is still relevant when considering experimental hypotheses for the post-zygotic barrier. Abnormal expression of imprinted genes has also been found in hybrids between flowering plant species [60]. Interestingly, hybrid seeds of A. thaliana and A. arenosa show increased viability when a mutation of the paternally expressed imprinted gene, PHE1, is present [60]. In flowering plants, endosperm breakdown in inter-specific hybrids has regularly been observed [61–63]. In this phenomenon, endosperm sizes are affected in a parent-of-origin dependent manner, which is also demonstrated in inter-ploidy crosses [64]. The endosperm abnormality caused by inter-specific and inter-ploidy crosses emerges at an early stage of endosperm development. After fertilization, the central cell undergoes several rounds of mitosis without cytokinesis and forms a syncytium. The syncytium then cellularizes [65], and the timing of cellularization is often altered in inter-specific and inter-ploidy crosses [4,66]; this timing alteration can be critical to phase transition during endosperm development [67]. In general, precocious cellularization results in a smaller endosperm, while delayed cellularization induces a larger endosperm. Based on analyses of many inter-specific crosses, several hypotheses have been proposed: “Endosperm balance number” in Solanum; “Polar nuclei activation” in Avena; and, “Ploidy barrier” in maize [64,68–70]. All of these proposals can be applied to other plant species. Although the molecular mechanism is still controversial [64,66,71], there is a general agreement that the degree of interaction of maternally and paternally contributed genomes determines this phenomenon [64]. 5 7. Conclusions In placental mammals and flowering plants, maternal nutritional flow to the embryo is provided from specialized tissues, namely the placenta and endosperm [6]. According to the parental conflict theory, maternally expressed imprinted genes repress nutritional flow to the embryo, and paternally expressed imprinted genes promote it [7,72]. Although there are exceptions, many of the imprinted genes in mammals and plants control development of the placenta and endosperm. They affect, therefore, nutritional flow to the embryo. In many studies, it has been shown that a proper balance between maternal and paternal contributions, determined by an epigenetic mechanism, is required for successful reproduction. Hence, mutation in imprinted genes induces abnormal development of placenta and endosperm, and consequently the embryos abort. This epigenetic mechanism may also be essential for reproductive barriers in placental organisms. Maternal and paternal contributions usually differ between species. If the regulatory mechanisms, copy number, activity of encoded proteins or affinity of protein–protein interactions were not equivalent in their genomic imprinting between these related species, then the developmental processes of the placenta and endosperm might be adversely affected. Uncovering the mechanism of genomic imprinting in different species will provide greater insights into the molecular frameworks of the reproductive barriers in the placenta and endosperm. Thus, the epigenetic mechanisms that we have described here might serve as an indicator of compatibility between species. Although no molecular mechanism was identified, a similar idea was proposed previously by both Nishiyama and Cooper [62,70]. Acknowledgements Funding on this topic is provided by a grant from the Ministry of Agriculture, Forestry and Fisheries of Japan (molecular cloning and characterization of agronomically important genes of rice, IPG0017) and by Grant-in-Aid for Scientific Research on Priority Areas (18075010) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. References [1] Arnaud P, Feil R. MEDEA takes control of its own imprinting. Cell 2006;124: 468–70. [2] Surani MA, Barton SC, Norris ML. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 1984;308: 548–50. [3] McGrath J, Solter D. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 1984;37:179–83. [4] Scott RJ, Spielman M, Bailey J, Dickinson HG. Parent-of-origin effects on seed development in Arabidopsis thaliana. Development 1998;125:3329–41. [5] Birchler JA. Dosage analysis of maize endosperm development. 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