Professor, Biology/Director of Center for Genomics & Bioinformatics
Office: Myers Hall 316C
Education: Ph.D. University of Wisconsin-Madison, 1999
Regulation of chromatin structure and gene expression by epigenetic modifications
Chromatin is the term used to describe DNA and associated packaging proteins (e.g. histones).Modifications of histones, such as methylation and acetylation at specific positions can cause the DNA to be packaged more tightly and become less transcriptionally active(heterochromatin), whereas other histone modifications can increase transcriptional activity by opening up the chromatin structure(euchromatin). These modifications are sometimes referred to as the;histone code; and play an important role in the regulation of gene expression in all eukaryotes. The sequences of histones, and in many cases histone-modifying enzymes, are highly conserved. Therefore, there is a high likelihood that the knowledge gained from research in model systems, will have broad applications in all eukaryotes.
In our laboratory, we use two different models to study the links between histone modifications, chromatin structure, and gene expression. The first model is the constitutive heterochromatin present in Arabidopsis nuclei. In wild-type nuclei, 8-10 spots of highly compacted heterochromatin are visible. These spots are called chromocenters and contain repetitive sequences, transposons, and rDNA genes. Histones in chromocenters are marked by modifications that are known to repress gene expression, such as histone H3 monomethylation at lysine 27 (H3K27me1). Our laboratory has identified ATXR5 and ATXR6 as the enzymes that are responsible for H3K27me1 at chromocenters and the loss of these enzymes leads to loss of gene silencing and decondensation of heterochromatin. Ongoing work in our lab is elucidating the mechanisms by which the activity of ATXR5 and ATXR6 is targeted to heterochromatin and how H3K27 methylation leads to gene silencing.
The second model that we use is an epigenetic switch that is triggered by signals from the environment. To ensure that flowering occurs at a favorable time of year, many plants growing in temperate climates have adopted a biennial growth habit. These plants contain a block to flowering that is eliminated by the prolonged cold temperatures of winter; thus flowering is prevented prior to winter and promoted in the favorable conditions of spring. In biennial-like, winter-annual accessions of Arabidopsis, this block to flowering is created by the floral repressor FLOWERING LOCUS C (FLC). Prior to winter, FLC is highly expressed and prevents flowering. Cold treatment, in turn, causes a permanent epigenetic shut off of FLC expression that is mediated by repressive histone modifications at the FLC locus. Our laboratory is actively involved in determining that molecular mechanisms that control this epigenetic switch.
Yannick Jacob, Elisa Bergamin, Mark T.A. Donoghue, Vanessa Mongeon, Chantal LeBlanc, Philipp Voigt, Charles J. Underwood, Joseph S. Brunzelle, Scott D. Michaels, Danny Reinberg, Jean-François Couture, and Robert A. Martienssen. 2014. Selective methylation of histone H3 variant H3.1 regulates heterochromatin replication. Science, 343: 1249-1253.
Ryan Over and Scott D. Michaels. 2014. Open and Closed: The Roles of Linker Histones. Molecular Plant, 7:481-491. (PMCID: PMC3941478)
Lei Ding, Sang Yeol Kim, and Scott D. Michaels. 2013. FLOWERING LOCUS C EXPRESSOR Family Proteins Regulate FLOWERING LOCUS C Expression in Both Winter-Annual and Rapid-Cycling Arabidopsis. Plant Physiology, 163: 243-252.
Hume Stroud, Christopher J. Hale, Suhua Feng, Elena Caro, Yannick Jacob, Scott D. Michaels and Steven E. Jacobsen. 2012. DNA methyltransferases are required to induce heterochromatic re-replication. PLoS Genet 8(7): e1002808. doi:10.1371/journal.pgen.1002808.
Guillaume Moissiard, Shawn J. Cokus, Joshua Cary, Suhua Feng, Allison C. Billi, Hume Stroud, Dylan Husmann, Ye Zhan, Bryan R. Lajoie, Rachel P. McCord, Christopher J. Hale, Wei Feng, Scott D. Michaels, Alison R. Frand, Matteo Pellegrini, Job Dekker, John K. Kim, and Steve Jacobsen. 2012. MORC family ATPases required for heterochromatin condensation and gene silencing. Science, 336: 1448-1451. (PMCID: PMC3376212)
Yannick Jacob, Hume Stroud, Chantal LeBlanc, Suhua Feng, Luting Zhuo, Elena Caro, Christiane Hassel, Crisanto Gutierrez, Scott D. Michaels and Steven E. Jacobsen. 2010. Two histone H3 lysine 27 methyltransferases, ATXR5 and ATXR6, regulate heterochromatic DNA replication. Nature, 466: 987-991. (PMCID: PMC2964344)