Plant Epigenetics Unit (Hidetoshi Saze)

Epigenetic Regulation of Gene Activity and Trans-generational Inheritance of Epigenetic Memory

Abstract

Genetic information on genomic DNA is faithfully replicated and transmitted to the two daughter cells through mitosis. However, for differential expression of genes in various cell lineages during development, or for prompt responses to environmental stimuli, organisms further utilize epigenetic mechanisms that generate additional layers of heritable information on chromosomes. Inheritance of the epigenetic information is mediated by modifications of chromatin, including DNA cytosine methylation, post-translational modifications of the core histone proteins and production of small RNA molecules. The epigenetic modifications can mediate both short-term (mitotic) and long-term (meiotic) transmission of active or inactive state of chromatin without changing the primary DNA sequence. Importantly, the epigenetic marks are heritable but potentially reversible, which therefore allow dynamic regulation of gene activities in response to surrounding environmental changes.

Plants offer ideal model systems for the studies of general epigenetic mechanisms and epigenetic inheritance of phenotypic variations. For instance, many epigenetic modifying factors found in other organisms are evolutionarily conserved in plants. Moreover, detailed profiles of genome-wide gene expression and epigenetic states of the genome (epigenome) in various environmental conditions are now available for the model plants such as Arabidopsis and rice. By taking both genetics and genomics approaches, we will explore the molecular mechanisms of epigenetic regulation of gene activity and trans-generational inheritance of epigenetic memory in plants.

Research Goals

By using the model plant Arabidopsis and other plant systems, we will address following key questions in epigenetics:

• How do cells distinguish between essential genes and parasitic transposons, and deposit the characteristic epigenetic modifications?
• What are the underlying molecular mechanisms of epigenetic inheritance of chromatin states through cell divisions, or over multiple generations?
• How much of the phenotypic variations or complex traits are attributed not to conventional “genotype” but to the plastic “epigenotype”? Do the epigenotypes ultimately contribute to the genome evolution?

Trans-generational epigenetic inheritance of phenotypic variations has been reported in many organisms including plants and animals. Since plants conserve a wide range of epigenetic modifications, our studies could also have broader implications for epigenetic regulation of genome integrity and phenotypic variations in other organisms.

References

Berthelier J, Furci L, Asai S, Sadykova M, Shimazaki T, Shirasu K, Saze H. (2023) Long-read direct RNA sequencing reveals epigenetic regulation of chimeric gene-transposon transcripts in Arabidopsis thaliana. Nat Commun. Jun 5;14(1):3248. doi: 10.1038/s41467-023-38954-z.

Miryeganeh M, Marlétaz F, Gavriouchkina D, Saze H. (2022) De novo genome assembly and in natura epigenomics reveal salinity-induced DNA methylation in the mangrove tree Bruguiera gymnorhiza. New Phytol. Mar;233(5):2094-2110. doi: 10.1111/nph.17738. Epub 2021 Oct 16.PMID: 34532854

Le NT, Harukawa Y, Miura S, Boer D, Kawabe A, Saze H. (2020) .Epigenetic regulation of spurious transcription initiation in Arabidopsis. Nat Commun. Jun 26;11(1):3224. doi: 10.1038/s41467-020-16951-w.

Espinas NA, Tu LN, Furci L, Shimajiri Y, Harukawa Y, Miura S, Takuno S, Saze H. (2020). Transcriptional regulation of genes bearing intronic heterochromatin in the rice genome. PLoS Genet. Mar 18;16(3):e1008637. doi: 10.1371/journal.pgen.1008637

Osabe K, Harukawa Y, Miura S, Saze H. (2017). Epigenetic Regulation of Intronic Transgenes in Arabidopsis. Sci Rep. Mar 24;7:45166. doi: 10.1038/srep45166.

Le ​Tu N., Miyazaki Y., Takuno S.,  Saze H. (2015). Epigenetic regulation of intragenic transposable elements impacts gene transcription in Arabidopsis thaliana. Nucleic Acids Res., doi: 10.1093/nar/gkv258

Saze H., Kitayama J, Takashima K, Miura S, Harukawa Y, Ito T, Kakutani T. (2013). Mechanism for full-length RNA processing of Arabidopsis genes containing intragenic heterochromatin. Nat. Commun., 4:2301.

Saze, H., Shiraishi, A., Miura, A., and Kakutani, T. (2008). Control of genic DNA methylation by a jmjC-domain containing protein in Arabidopsis thaliana. Science 319, 462-465.

Saze, H. (2008). Epigenetic Memory Transmission through Mitosis and Meiosis in Plants. Semin. Cell Dev. Biol. 19, 527-536.

Saze, H., and Kakutani, T. (2007). Heritable epigenetic mutation of a transposon-flanked Arabidopsis gene due to lack of the chromatin-remodeling factor DDM1. EMBO J. 26, 3641-3652.

Saze, H., Mittelsten-Scheid, O., and Paszkowski, J. (2003). Maintenance of CpG methylation is essential for epigenetic inheritance during plant gametogenesis. Nat. Genet. 34, 65-69.