The transition from vegetative development to flowering is a major event in the life cycle of plants. Stem cells in the shoot apical meristem switch from producing primordia that will give rise to the vegetative parts of the plant (e.g., leaves) to produce the reproductive structures (flowers). Thus flowering is an excellent system for studying how undifferentiated cells choose between alternative fates. Because proper timing of this transition is critical to reproductive success, it is highly regulated by both environmenta and endogenous factors. These cues allow plants to flower at a favorable time of year and at an appropriate stage of development. One key regulator of flowering time in Arabidopsis is FLOWERING LOCUS C (FLC), a MADS-domain-containing transcription factor that acts to delay flowering. The transcriptional regulation of FLC is highly complex. Late- flowering winter-annual strains contain active alleles of FRIGIDA (FRI) that cause FLC to be highly expressed. Through a process known as vernalization, however, FLC expression can be epigenetically silenced by a long period of cold exposure (e.g., winter). This system prevents winter-annual Arabidopsis from flowering prior to winter and promotes spring flowering. Rapid-cycling strains, in contrast, are naturally occurring null mutants for fri and flower early without vernalization. I these stains, FLC expression is repressed by a group of genes known collectively as the autonomous floral-promotion pathway. The autonomous pathway is required for the Polycomb Repressor Complex 2 (PRC2) to deposit repressive histone H3 lysine 27 trimethylation (H3K27me3) at FLC chromatin. The details of how the autonomous pathway facilitates PRC2 action remain unknown. The putative functions of the autonomous-pathway proteins (chromatin remodeling and RNA-binding/processing), however, suggest a link between RNA metabolism and chromatin remodeling. We propose a comprehensive set of genetic, genomic, and biochemical approaches to determine the molecular mechanism of the autonomous pathway. The fact that homologs of PRC2 and many of the autonomous pathway proteins exist in both plants and animals suggests that this mechanism is evolutionarily conserved and that our findings are likely to have broad impacts for understanding gene regulation in both plants and animals.

Public Health Relevance

Proper gene regulation is essential for development and the specification of tissue types;consequently, missexpression is associated with birth defects and many diseases (including cancer). DNA-packaging proteins, called histones, undergo extensive post- translational modification and these modifications comprise one of the primary mechanisms controlling gene expression in all eukaryotes. A complete understanding of how individual genes are targeted by histone modifying enzymes and how these modifications stimulate or repress gene expression is essential to our understanding of development and disease.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Haynes, Susan R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University Bloomington
Schools of Arts and Sciences
United States
Zip Code
Bergamin, Elisa; Sarvan, Sabina; Malette, Josée et al. (2017) Molecular basis for the methylation specificity of ATXR5 for histone H3. Nucleic Acids Res 45:6375-6387
Feng, Wei; Hale, Christopher J; Over, Ryan S et al. (2017) Large-scale heterochromatin remodeling linked to overreplication-associated DNA damage. Proc Natl Acad Sci U S A 114:406-411
Hale, Christopher J; Potok, Magdalena E; Lopez, Jennifer et al. (2016) Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. PLoS Genet 12:e1006092
Feng, Wei; Michaels, Scott D (2015) Accessing the Inaccessible: The Organization, Transcription, Replication, and Repair of Heterochromatin in Plants. Annu Rev Genet 49:439-59
Over, Ryan S; Michaels, Scott D (2014) Open and closed: the roles of linker histones in plants and animals. Mol Plant 7:481-91
Jacob, Yannick; Bergamin, Elisa; Donoghue, Mark T A et al. (2014) Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication. Science 343:1249-53
Lovell, John T; Juenger, Thomas E; Michaels, Scott D et al. (2013) Pleiotropy of FRIGIDA enhances the potential for multivariate adaptation. Proc Biol Sci 280:20131043
Ding, Lei; Kim, Sang Yeol; Michaels, Scott D (2013) FLOWERING LOCUS C EXPRESSOR family proteins regulate FLOWERING LOCUS C expression in both winter-annual and rapid-cycling Arabidopsis. Plant Physiol 163:243-52
Pontvianne, Frédéric; Blevins, Todd; Chandrasekhara, Chinmayi et al. (2012) Histone methyltransferases regulating rRNA gene dose and dosage control in Arabidopsis. Genes Dev 26:945-57
Stroud, Hume; Hale, Christopher J; Feng, Suhua et al. (2012) DNA methyltransferases are required to induce heterochromatic re-replication in Arabidopsis. PLoS Genet 8:e1002808

Showing the most recent 10 out of 28 publications