COLD SPRING HARBOR LABORATORY
Grant: $336,000 - National Institutes of Health - Sep. 15, 2009
No votes have been cast for this award yet
Join the conversation: Post a comment about this award
Award Description: Heterochromatin was first discovered in plants, but is widespread among eukaryotes and has important roles in chromosome structure, centromere function, gene expression and transposon silencing. Transposable elements (TEs) are major constituents of heterochromatin and are subject to transcriptional silencing through histone and DNA modification, guided by the chromatin remodeler DECREASE IN DNA METHYLATION1 (DDM1) in Arabidopsis, and its mammalian homolog Lsh1, both of which are expressed at high levels in germ cells. We have found that TEs in Arabidopsis are activated in the vegetative nucleus of the pollen grain, a terminally differentiated 'support' cell that completely encloses the sperm cells before fertilization. In WT pollen grains and in ddm1 mutant plants, 24nt small RNA from centromeric retrotransposons are replaced by large amounts of 21-22nt small RNAs. DDM1 is not expressed in the vegetative nucleus, explaining why similar reactivation of TEs and 21nt small RNAs occur in both pollen and ddm1. We will investigate the proposition that these novel 21nt siRNA guide silencing of any active elements in sperm cells via transport from the surrounding pollen grain. The proposed mechanism is reminiscent of piRNA-mediated TE regulation in the mammalian germline, and of interactions between micronuclei and macronuclei in ciliates. Some TE- derived siRNAs in pollen and ddm1 mutants target specific genes for methylation resulting in epialleles; epialleles are well known in ddm1 mutants, but also in cancer cells, in which TEs are activated epigenetically and tumor suppressor genes are silenced. We will use a combination of forward and reverse genetic screens to further dissect this pathway, and hope to shed light on the conserved role of heterochromatin and TEs in RNAi-mediated silencing, chromosome organization and germ cell differentiation in animals and plants. PUBLIC HEALTH RELEVANCE: Heterochromatin is composed of transposons and satellite repeats in almost all higher eukaryotes, but its function remains a mystery. In Arabidopsis we have found that retrotransposons inserted into heterochromatin generate large amounts of 21nt small RNA in the vegetative nucleus of pollen grains, where transposons are actively transcribed. These small RNA are found throughout the plant in mutants of the chromatin remodeler Decrease in DNA methylation 1 (DDM1). . We will investigate the biogenesis of these small RNAs, and the proposition that they silence transposons in sperm cells, reminiscent of piwi RNA in animal germline. In addition to the transposable element small RNAs, 21nt small RNAs matching methylated genes (epialleles) arise in the ddm1 background. These genic sRNAs may be responsible for sporadic gene methylation (epialleles) in ddm1. Cancer cells have similar changes in DNA methylation, which may use the same mechanism.
Project Description: Not yet started.
Jobs Summary: None (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 15, 2009. Help expand these official descriptions using the wiki below.
No comments have been added for this project.