The germlines of plants and animals undergo genome reprogramming in order to reset epigenetic marks that would otherwise interfere with pluripotency of the zygote. Perhaps chief among these marks are epigenetic modifications of transposable elements (TE), which make up a majority of most eukaryotic genomes. We have found that small interfering RNA derived from heterochromatin plays a key role in germline reprogramming in plants, and there is mounting evidence for a similar phenomenon in animals. Germ cells in plants differentiate from the products of meiosis by mitotic division, along with companion cells that resemble nurse cells and other support cells in animals. We have found that reprogramming of the pollen grain companion cell nucleus (the vegetative nucleus or VN) results in transposon activation, and that a new class of epigenetically activated small interfering RNA (easiRNA) accumulate in sperm cells, that have the potential to silence these same transposons. We have recently found that genome reprogramming depends on DNA methylation, but also on the deposition and modification of specific histone variants, that is likey the result of cell cycle dependent chromatin remodeling. Epigenetic inheritance is far more widespread in plants than in mammals, although the mechanisms are largely conserved, so that plants provide an excellent system to study their origin. We will investigate the mechanism of germline reprogramming in plants, and the transgenerational consequences when reprogramming goes awry.

Public Health Relevance

There is a growing body of evidence that environmental factors can have transgenerational effects on human health. However, the mechanism of epigenetic transmission and its impact on gene expression in the next generation is still unknown. Genome reprogramming is fundamental to normal development of the germline and early embryo. Both primordial germ cells and embryos lose DNA methylation from transposons, and gain methylation of imprinted genes. Similar reprogramming of the cancer genome can lead to silencing of tumor suppressor genes. Focusing on plants, we have found mobile small RNA signals from transposons that arise following reprogramming in the germline. These small RNA depend on the chromatin remodeler Decrease in DNA Methylation1which, like its homologs in mouse and humans, is expressed in sperm cells, and a similar interaction between small RNA, transposon silencing and genome reprogramming has recently emerged in the mammalian germline. By manipulating key reprogramming mechanisms, such as DNA methylation and chromatin remodelling, we will determine how these small RNA contribute to epigenetic inheritance.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM067014-12
Application #
9129683
Study Section
Molecular Genetics B Study Section (MGB)
Program Officer
Carter, Anthony D
Project Start
2003-08-01
Project End
2019-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
12
Fiscal Year
2016
Total Cost
$368,640
Indirect Cost
$176,640
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
Borges, Filipe; Parent, Jean-Sébastien; van Ex, Frédéric et al. (2018) Transposon-derived small RNAs triggered by miR845 mediate genome dosage response in Arabidopsis. Nat Genet 50:186-192
Underwood, Charles J; Choi, Kyuha; Lambing, Christophe et al. (2018) Epigenetic activation of meiotic recombination near Arabidopsis thaliana centromeres via loss of H3K9me2 and non-CG DNA methylation. Genome Res 28:519-531
Underwood, Charles J; Henderson, Ian R; Martienssen, Robert A (2017) Genetic and epigenetic variation of transposable elements in Arabidopsis. Curr Opin Plant Biol 36:135-141
Ziolkowski, Piotr A; Underwood, Charles J; Lambing, Christophe et al. (2017) Natural variation and dosage of the HEI10 meiotic E3 ligase controlArabidopsiscrossover recombination. Genes Dev 31:306-317
Chomet, Paul; Martienssen, Rob (2017) Barbara McClintock's Final Years as Nobelist and Mentor: A Memoir. Cell 170:1049-1054
Schorn, Andrea J; Gutbrod, Michael J; LeBlanc, Chantal et al. (2017) LTR-Retrotransposon Control by tRNA-Derived Small RNAs. Cell 170:61-71.e11
Ingouff, Mathieu; Selles, Benjamin; Michaud, Caroline et al. (2017) Live-cell analysis of DNA methylation during sexual reproduction in Arabidopsis reveals context and sex-specific dynamics controlled by noncanonical RdDM. Genes Dev 31:72-83
Quadrana, Leandro; Bortolini Silveira, Amanda; Mayhew, George F et al. (2016) The Arabidopsis thaliana mobilome and its impact at the species level. Elife 5:
Fransz, Paul; Linc, Gabriella; Lee, Cheng-Ruei et al. (2016) Molecular, genetic and evolutionary analysis of a paracentric inversion in Arabidopsis thaliana. Plant J 88:159-178
Borges, Filipe; Martienssen, Robert A (2015) The expanding world of small RNAs in plants. Nat Rev Mol Cell Biol 16:727-41

Showing the most recent 10 out of 53 publications