Research
Epigenetic mechanisms of gene control, chromosome structure and function 

We’re interested in mechanisms that generate and maintain heritable phenotypic variation. Our current emphasis is aimed at understanding epigenetic systems that cause mitotically, and meiotically, heritable changes in gene activity. We are focusing on one particular mechanism, called paramutation, in which the regulation of one allele is heritably altered through interactions with the homologous allele.  We are asking several key questions: what is the molecular nature of this meiotically heritable change, how does this change affect gene expression, how do two alleles communicate with each other, and how general is this mechanism in plant growth and development? We use the superb genetic, molecular genetic, cytogenetic, and cytological tools available in Zea mays to address these questions.

Our general strategy is to identify molecular and cellular components required for paramutation and then use these as tools to further understand the genomic and chromosome dynamics involved. We use the well-defined anthocyanin pigment pathway as our simple model system. Plant color in maize is quantitatively controlled by action of the purple plant1 (pl1) gene. One particular pl1 allele (Pl) can exist in distinct transcription states. In the figure below, note tassels of sibling maize plants displaying two distinct epigenetic expression states of the Pl allele. Darkly colored anthers reflect high levels of pl1 transcription and lightly colored anthers indicate a repressed transcription state.

Highly transcribed Pl alleles are invariably repressed when exposed to a repressed Pl allele (denoted Pl’) in a heterozygote. Genetic and molecular observations suggest that paramutation reflects alterations in chromatin structure that are sensitive to chromosome pairing interactions.

We’ve begun to identify important components of the paramutation system using genetic analyses. Seedling-based screens identify mutations in critical cis-acting sequences and a novel class of trans-acting rmr (required to maintain repression) loci that allow heritable restoration of high levels of pl1 gene action. Several rmr genes also play crucial roles in growth and development. Cloning of these rmr loci by positional approaches has begun to highlight novel roles for alternative DNA-dependent RNA polymerases that affect meiotically heritable changes in transcriptional control. We are currently taking both biochemical and genomic approaches to understand the operation of this novel regulatory system in plant development and homeostasis.

Recent Publications

• Hollick JB. Paramutation and related phenomena in diverse species. Nat Rev Genet. 2017 Jan;18(1):5-23. doi: 10.1038/nrg.2016.115.

• Giacopelli BJ, Hollick JB. Trans-homolog interactions facilitating paramutation in Zea mays. Plant Phys 168: 1226-1236. DOI:10.1104/pp15.00591.

• Gabriel JM, Hollick JB. 2015 Paramutation in maize and related behaviors in metazoans.  Sem Cell Dev Biol 44: 11-21. DOI:10.1016/j.semcdb.2015.08.008. 

• Erhard KF, Talbot JRB, Deans NC, McClish AC, Hollick JB. 2015 Nascent transcription affected by RNA  polymerase IV in Zea mays. Genetics 199: 1107-1125. DOI:10.1534/genetics.115.174714.

• Erhard KF, Parkinson SE, Gross SM, Barbour JR, Lim JP, Hollick JB. 2013  Maize RNA polymerase IV defines trans-generational epigenetic variation. Plant Cell 25: 808-819. published online March 23, 2013 DOI 10.1105/tpc.112.107680.

• Hollick JB. 2012 Paramutation: a trans-homolog interaction affecting heritable gene regulation. Curr Opin Plant Biol 15: 536-543. DOI 10.1016/j.pbi.2012.09.003.

• Barbour JR, Liao IT, Stonaker JL, Lim JP, Lee CC, Parkinson SE, Kermicle J, Simon SA, Meyers BC, Williams-Carrier R, Barkan A, Hollick JB. 2012  required to maintain repression2 is a novel protein that facilitates locus-specific paramutation in maize. Plant Cell published online May 4, 2012 DOI 10.1105/tpc.112.097618. PDF 2036K

• Erhard, KF and Hollick, JB. 2011  Paramutation: a process for acquiring trans-generational regulatory states. Curr Opin Plant Biol 14: 210-216  doi:10.1016/j.pbi.2011.02.005. PDF 337K

• Hollick, J.B. 2010 Paramutation and Development. Ann. Rev. Cell Dev. Biol. 26:26.1-26.23. doi:10.1146/annurev.cellbio.042308.113400 PDF 1853 kb

• Stonaker, J.L., Lim, J.P., Erhard, K.F., Hollick, J.B. 2009 Diversity of Pol IV function is defined by mutations at the maize rmr7 locus. PLoS Genetics 5(8): e1000706. doi:10.1371/journal.pgen.1000706 PDF 323 kb

• Hale, C.J., Erhard, K.F., Lisch, D., Hollick, J.B. 2009 Production and processing of siRNA precursor transcripts from the highly repetitive maize genome. PLoS Genetics 5(8): e1000598. doi:10.1371/journal.pgen.1000598 PDF 1434 kb

• Erhard, K.F. Jr., Stonaker, J.L., Parkinson, S.E., Lim, J.P., Hale, C.J., Hollick, J.B. (2009) RNA Polymerase IV functions in paramutation in Zea mays. Science 323: 1201-1205.

• Hollick, J.B., (2008) Sensing the epigenome. Trends in Plant Sci. 13(7): 398-404. PDF 339 kb

• Hale, C.J., Stonaker, J.L., Gross, S.M. and Hollick, J.B. (2007) A novel Snf2 protein maintains trans-generational regulatory states established by paramutation in maize. PLoS Biol 5(10): 2156-2165 e275. PDF 663 kb

• Parkinson, S.E., Gross, S.M. and Hollick, J.B. (2007) Maize sex determination and abaxial leaf fates are canalized by a factor that maintains repressed epigenetic states. Dev Biol 308: 462-473. PDF 1739 kb

• Gross, S.M and Hollick, J.B. (2007) Multiple trans-sensing interactions affect meiotically heritable epigenetic states at the pl1 locus. Genetics 176: 829-839. PDF 1199 kb

• Hollick, J.B., Kermicle, J.L. and Parkinson, S.E. (2005) Rmr6 maintains meiotic inheritance of paramutant states in Zea Mays. Genetics 171: 725-740. PDF 386 kb

• Hollick, J.B. (2003) Paramutation in Plants. Encyclopedia of Life Sciences. April 2003. PDF 1334 kb

• Hollick, J.B. and Chandler, V.L. (2001) Genetic factors required to maintain repression of a paramutagenic maize pl1 allele. Genetics 157: 369-378. PDF 310 kb

• Dorweiler, J.D., Carey, C.C., Kubo, K.M., Hollick, J.B., Kermicle, J., Chandler, V.L. (2000) Mediator of paramutation 1 is required for the establishment and maintenance of paramutation at multiple maize loci. The Plant Cell 12 (11): 2101-2118. PDF 467 kb

• Hollick, J.B., Patterson, G.I, Asmundsson, I.M., Chandler, V.L. (2000) Paramutation alters regulatory control of the maize pl locus. Genetics 154: 1827-1838. PDF 342 kb

• Hollick, J.B. and Chandler, V.L. (1998) Epigenetic allelic states of a transcriptional regulatory locus exhibit overdominant gene action. Genetics 150: 891-897.

• Hollick, J.B., Dorweiler, J.E., Chandler, V.L. (1997) Paramutation and related allelic interactions. Trends in Genetics 13 (8): 302-307.

• Chandler, V.L., Kubo, K.M., Hollick, J.B. (1996) b and pl paramutation in maize: heritable transcription states programmed during development, In Epigenetics. R. Martienssen, A. Riggs, and V.E.A. Russo eds., Cold Spring Harbor Press, pp 289-304.

• Hollick, J.B., Patterson, G.I., Coe, E.H., Cone, K.C., Chandler V.L. (1995) Allelic interactions heritably alter the activity of a metastable maize pl allele. Genetics 141: 709-719