Eukaryotic gene regulation is a very complex process in which a wide range of molecules and mechanisms come together, such as different types of DNA sequences, proteins and RNAs, genetic and epigenetic mechanisms. The tremendously rapid advances in high-throughput sequencing, but also advances in other techniques have enabled many exciting new discoveries in the field of gene regulation. Research in my team focuses on gene regulation through cis-regulatory sequences, and epigenetic and chromatin-based mechanisms. We use plants (maize, tomato, Arabidopsis, and oilseed rape) as a model system and mainly focus on two research lines: 1) Regulation by epigenetic mechanisms & chromatin structure, 2) Control of gene expression by cis-regulatory sequences.
Regulation by epigenetic mechanisms & chromatin structure
Plant and animal breeding has been done for thousands of years and forms the basis of food production and other human activities. It is based on the heritability of desirable traits and the reiterated process of crossing and selection. Most differences in heritable traits are due to genetic variation, which are DNA sequence differences between individuals. In addition, epigenetic variation can result in trait variation and contribute to the diversity we know of today. Epigenetic variation refers to mitotically and/or meiotically heritable changes in genome function based on chromatin modifications instead of changes in the DNA sequence. Examples of such modifications are DNA methylation and histone modifications. Epigenetic modifications are heritable, but not as stable as the genetic code. At particular DNA sequences the epigenetic information can be remodeled, among others under the influence of homologous DNA sequences carrying different epigenetic marks. The latter is well known to occur between individual alleles in a process called paramutation, but has also been indicated to occur at a genome-wide scale in heterosis, a phenomenon extensively exploited in agricultural breeding in which F1 hybrids between two parents display superior phenotypes compared to that of their parents. Currently, the contribution of epigenetic variation to beneficial traits displayed by crop plants and livestock, as well as the molecular basis underlying heterosis are still largely unknown. The aim of this research line is to unravel the mechanisms underlying the transfer of epigenetic information, both between specific alleles as genome-wide.
Control of gene expression by cis-regulatory sequences.
The differentiation of cells and their response to external signals such as light, temperature and pathogens is largely accomplished through the activation and repression of regulatory DNA sequences such as transcriptional enhancers at the correct moment in time and space (Schmitz et al, 2022). Enhancers are non-coding DNA sequences that activate the transcription of genes located up to several Mb away. Knowledge on the transcriptional regulatory code is crucial for the functional annotation of the genome and the selection of desirable traits for plant breeding. The regulatory code of plants, especially that of crop plants, is however still largely unknown. Genome-wide approaches have identified thousands of enhancers in animals, but are only very recently being applied to plants. This line of research is focused on unravelling the regulatory code of crop plants in general, and that of Zea mays in particular. Current and future work is focused on the identification and characterization of regulatory sequences and their target genes. This work contributes to a better understanding of the regulatory code in plants, and will enlarge the toolbox for the functional annotation and characterization of complex genomes, and promises new targets for informed breeding in crop plants.
There are possibilities for students to do an internship in my group. Please enquire for the projects currently available. Every internship will involve a range of techniques. Techniques to be used are amongst others recombinant DNA technology, regular and quantitative PCR, RT-qPCR, protoplast transformation, plant transformation, etc.
22. Louwers, M., Splinter, E., de Laat, W., Haring, M., Bader, R., van Driel, R., Stam, M.(2007) Long-distance chromatin looping within the maize b1 locus. Chromosome Research 12, Suppl 2, 19. |
21. Haring M, Offermann S, Danker T, Horst I, Peterhaensel C, Stam M. (2007) Chromatin immunoprecipitation: optimization, quantitative analysis and data normalization. Plant Methods, 3, 11. |
20. Louwers, M., Haring, M. and Stam, M. (2005) When alleles meet: Paramutation. In P. Meyer, ed, Plant Epigenetics. Blackwell Publishing Ltd, Oxford, UK, 134-173. |
19. Stam M., Mittelsten Scheid O. (2005) Paramutation: an encounter leaving a lasting impression. TIPS 10, 283-290. |
18. Chandler V.L., Stam M. (2004) Chromatin conversations: mechanisms and implications of paramutation. Nat Rev Genet. 5, 532-44. |
17. Chandler, V.L., Stam, M. and Sidorenko, L.V. (2002) Long distance cis and trans interactions mediate paramutation. In: Advances in Genetics, Vol. 46. J.C. Dunlap and C.-ting Wu. Academic Press, San Diego, USA, pp. 215-234. |
16. Stam, M., Belele, C., Ramakrishna, W., Dorweiler, J., Bennetzen, J. and Chandler, V.L. (2002) The regulatory regions required for B’ paramutation and expression are located far upstream of the maize b1 transcribed sequences. Genetics 162, 917-930. |
15. Stam, M., Belele, C., Dorweiler, J and Chandler, V.L. (2002) Differential chromatin structure within a tandem array 100 kb upstream of the maize b1 locus is associated with paramutation. Genes and Development 16, 1906-1918. |
14. Stam, M., T. Lavin and V. Chandler (2000) Npi402 and ncsu1 are identical; inra1 (tmp) maps upstream of the b promoter. Maize Genetics Coop Newsl. 74: p. 66-67. |
13. Stam, M., de Bruin, R., Van Blokland, R., Van der Hoorn, R.A.L., Mol, J.N.M. and Kooter, J. (2000) Distinct features of post-transcriptional gene silencing by antisense transgenes in single copy and inverted T-DNA repeat loci. Plant J. 21, 27-42. |
12. Jorgensen, R. A., Que, Qiudeng and Stam, M. (1999) Do unintended antisense transcripts contribute to sense co-suppression in plants? Trends in Genet. 15, 11-12. |
11. Stam, M., Viterbo, A., Mol, J. N.M. and Kooter, J.M. (1998) Position-dependent methylation and transcriptional silencing of transgenes in inverted T-DNA repeats. Implications for posttranscriptional silencing of homologous host genes in plants. Mol Cell Biol 18, 6165-6177. |
10. Stam, M., de Bruin, R., Kenter, S., van der Hoorn, R.A.L., van Blokland, R., Mol, J N.M. and Kooter, J.M. (1997) Post-transcriptional silencing of endogenous genes in Petunia by inverted transgene repeats. Plant J. 12, 63-82. |
9. Stam, M., Mol, J.N.M and Kooter, J.M. (1997) The silence of genes in transgenic plants. Annals of Botany 79, 3-12. |
8. Van Blokland, R., Van der Geest, N., De Lange, P., Stam, M., Mol, J.N.M. and Kooter, J.M. (1996) Post-transcriptional suppression of chalcone synthase genes in Petunia hybrida and the accumulation of unspliced pre-mRNAs. In: Mechanisms and Applications of Gene Silencing. D. Grierson, G.W. Lycett and G.A. Tucker. Nottingham: Nottingham University Press, pp. 57-69. |
7. Kunz, C., Schöb, H., Stam, M., Kooter, J.M. and Meins, Jr. (1996) Developmentally regulated silencing and reactivation of tobacco chitinase transgene expression. Plant J. 10, 437-450. |
6. Fransz, P.F., Stam, M., Montijn, B., TenHoopen, R., Wiegant, J., Kooter, J.M/, Oud, O. and Nanninga, N (1996) Detection of single copy genes and chromosome rearrangements in Petunia hybrida by fluorescence in situ hybridization. Plant J. 9, 767-774. |
5. Van Aarssen, R., Soetaert, P., Stam, M., Dockx, J., Gosselé, V., Seurinck, J, Reynearts, A. and Cornelissen (1995) cry IA(b) transcript formation in tobacco is inefficient. Plant Mol. Biol. 28, 513-524. |
4. Mol, J.N.M., van Blokland, R., de Lange, P., Stam, M. and Kooter, J.M. (1994) Post-transcriptional inhibition of gene expression: sense and antisense genes. In J Paszkowski, ed, Homologous Recombination and Gene silencing in Plants. Kluwer, Dordrecht, The Netherlands, pp 309-334. |
3. Kooter, J.M., Van Blokland, R., de Lange, P., Stam, M. and Mol, J.N.M. (1993). The use of antisense and sense genes to generate mutant phenotypes: Suppression of flower pigmentation in Petunia. Proceedings XVI Journées Internationales du Groupe Polyphenols. |
2. Van der Meer, I.M., Stam, M.E., van Tunen, A.J., Mol, J.N.M. and Stuitje, A.R. (1992) Inhibition of flavonoid biosynthesis in Petunia anthers by antisense RNA: a novel way to engineer nuclear male sterility. In: Angiosperm pollen and ovules, basic and applied aspects. E. Ottaviano, D.L. Mulcahy, M. Sari Gorla and G. Bergamini Mulcahy, eds. Springer-Verlag New York, Inc., 175 Fifth Avenue, New York, NY 10010, USA, pp 22-27. |
1. Van der Meer, I.M., Stam, M.E., van Tunen, A.J., Mol, J.N.M. and Stuitje, A.R. (1992) Antisense inhibition of flavonoid biosynthesis in petunia anthers results in male sterility. Plant Cell 4, 253-262. |
Patent application
"MODIFIED BT GENE II"- Invention: Cornelissen, Soetaert, Stam, Dockx- Plant Genetic Systems n.v., filed in USA and Canada, PCT/EP 91/00733; EP 91402920.2; EP 92400820.4; PCT/EP92/02547; PCT/EP92/02547.
Title Project: Unraveling the mechanisms underlying paramutation at the maize B-I and B' alleles
r.bader@uva.nl
Title Project: Quantitative relationships between chromatin looping and gene activity
Systems Biology Project University of Amsterdam
I.Hovel@uva.nl
Title project: The role of Epigenetic regulation and chromosomal interactions in hybrid vigour
CIPY project, http://www.cipy.nl
K.Lauss@uva.nl
Title project: Epigenetics meets targeted mutagenesis
Open Technology Program of STW, project in close collaboration with KeyGene (Wageningen, The Netherlands)
m.tark@uva.nl
Title project: Epigenetics meets targeted mutagenesis
Open Technology Program of STW, project in close collaboration with KeyGene (Wageningen, The Netherlands)
D.T.Anggoro@uva.nl
Picture will follow soon
Title project: Epigenetic regulation of economically important plant traits
EU-FP7 Marie Curie ITN EpiTRAITS
Picture will follow soon
Max Haring
Marieke Louwers
Joke van Bemmel (2004-2005)
Yan Yang (2005)
Mara de Sain (2007-2008)
Gerben Marsman (2008)
Michael Ignarski (2008-2009)
Pegah Poorfaraj (2009-2010)
Bas Jansen (2011)
Erica Geers (2005-2006)
Elisa Teunissen (2006)
Annemarie Castricum (2011-2012)