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Dr. M.E. (Maike) Stam

Faculty of Science
Swammerdam Institute for Life Sciences
Photographer: Maike Stam

Visiting address
  • Science Park 904
  • Room number: C2.106
Postal address
  • Postbus 1210
    1000 BE Amsterdam
  • Profile

    Epigenetic and chromatin regulation of gene expression

    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.

     

    Figure 1. Paramutation, the transfer of heritable silencing information between two alleles, results in silencing of susceptible alleles by inducing alleles. Paramutation requires multiple components of the RNA-directed DNA methylation (RdDM) pathway, which is characterized by 24nt siRNAs and CHH methylation. With paramutation at the maize b1 gene, affecting plant pigmentation, the low expressed B’ epiallele heritably changes the high expressed B-I epiallele into B’ with 100% frequency. Seven 853 bp tandem repeats (hepta-repeat) 100kb upstream of b1 are required for paramutation and high b1 expression.

    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.

     

    Figure 2. Chromatin interactions between distal CRMs and their target gene affect gene expression levels. An example of chromatin interactions at the maize b1 locus that positively correlate with b1 expression levels. The Booster-Intense (B-I) allele contains the b1 hepta-repeat enhancer 100 kbp upstream of the b1 gene, and other putative regulatory sequences ~-15, -45 and -107 kbp upstream. In seedling tissue of B-I plants, the b1 gene is low expressed, low H3K9ac and H3K27me2 levels are observed at the gene body, and low H3K27me2 levels at the repeat enhancer. Upon transcriptional activation of b1 in husk tissue, nucleosomes and H3K27me2 are lost at the enhancer and gene, H3K9ac levels are increased, and the repeat enhancer and regions ~-15, -45 and -107 kbp upstream physically interact with each other and the TSS of b1, resulting in enhanced b1 expression. Light blue triangles, histone acetylation; dark blue octagonal shapes, H3K27me2; grey barrels, nucleosomes; green circles, transcription factor.

    Figure 2. Chromatin interactions between distal CRMs and their target gene affect gene expression levels. An example of chromatin interactions at the maize b1 locus that positively correlate with b1 expression levels. The Booster-Intense (B-I) allele contains the b1 hepta-repeat enhancer 100 kbp upstream of the b1 gene, and other putative regulatory sequences ~-15, -45 and -107 kbp upstream. In seedling tissue of B-I plants, the b1 gene is low expressed, low H3K9ac and H3K27me2 levels are observed at the gene body, and low H3K27me2 levels at the repeat enhancer. Upon transcriptional activation of b1 in husk tissue, nucleosomes and H3K27me2 are lost at the enhancer and gene, H3K9ac levels are increased, and the repeat enhancer and regions ~-15, -45 and -107 kbp upstream physically interact with each other and the TSS of b1, resulting in enhanced b1 expression. Light blue triangles, histone acetylation; dark blue octagonal shapes, H3K27me2; grey barrels, nucleosomes; green circles, transcription factor.

     

     

    SILS
    Figure 3. One of our model systems is maize

    Student Projects

    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.

  • Publications until 2007

    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.

  • Lab members

    Current Labmembers

    Rechien Bader

    Research Technician & Labmanager since 2002. Rechien works on several projects, including projects on paramutation and regulatory sequences in Zea Mays. r.bader@uva.nl

    Kevin Peek

    PhD student since 2022. Kevin is appointed on an EPS proposal granted in the TKI Graduate School Green Top sectors. The title of his project is: Stabilizing unstable traits: elucidating the mechanisms underlying non-mendelian segregation in crops. k.peek@uva.nl

    Open Position (recruitment opens September 1; EpiSeedLink.eu).

    This position is part of the EU Marie Skłdowska-Curie Doctoral Network EpiSeedLink, acronym for: ‘From seed to seedling: Epigenetic mechanisms of priming to design strategies for crop improvement’. The EpiSeedLink consortium comprises 9 research teams and two industrial stakeholders across Europe and will recruit 11 PhD students. The title of the project in the Stam group is: Identification of oilseed rape cis-regulatory elements involved in drought resistance.

    Lorenzo Reggiani

    Erasmus MSc student July-Dec 2022. Lorenzo works on the same project as Kevin.

     

    Former labmembers

    Victor Sánchez Camargo

    Postdoc from 2022-2021. Victor worked among others on the identification andcharacterization of cis-regulatory sequences by ATAC-seq and transient expression.

    Labday out May 2018

    Blaise Weber

    PhD student from 2013-2017. Blaise was supported by the European Commission Seventh Framework People-2012-ITN project EpiTRAITS, GA-316965, which was coordinated by Maike Stam. Blaise worked on the Identification and validation of maize enhancers, and defended his thesis in 2018.

    Rurika Oka

    Early stage researcher from 2014-2017. Rurika was supported by the European Commission Seventh Framework People-2012-ITN project EpiTRAITS, GA-316965, which was coordinated by Maike Stam. Rurika worked as a bioinformatician on the Identification of maize enhancers.

    Marie Curie ITN EpiTRAITS (coordinated by Maike Stam): PhD students, postdocs & PIs at the start-up meeting in Amsterdam March 2013
    Christmas breakfast 2012

    Iris Hövel

    PhD student from 2012-2016. The title of Iris’ thesis is ‘Novel insight into gene silencing mechanisms in Zea Mays and Arabidopsis thaliana’. She defended her thesis June 8, 2016. This project was a Systems Biology Project funded by the University of Amsterdam.

    Kathrin Lauss

    PhD student from 2012-2016. The title of Kathrin’s thesis is: ‘Phenotypic variation in plants: roles for epigenetics’. The project was funded by the Centre for Improving Plant Yield (CIPY), which was part of the Netherlands Genomics Initiative in the Netherlands. Kathrin defended her thesis January 11, 2017.

    Mariliis Tark-Dame

    Post-doc from 2012-2017. Mariliis worked on the STW project: Epigenetics meets targeted mutagenesis. This project was a project in close collaboration with KeyGene (Wageningen, The Netherlands). 

    Damar Anggoro

    Research Technician from 2012-2017. Damar worked on the STW project: Epigenetics meets targeted mutagenesis. This project was a project in close collaboration with KeyGene (Wageningen, The Netherlands). 

     

    Labday out, July 2006

    Marieke Louwers

    PhD student from 2003-2008. The title of Marieke’s thesis is: ‘Chromatin looping and epigenetic regulation at the maize b1 locus’. Marieke defended her thesis Sept 4, 2008.  She was paid by the University of Amsterdam.

     

    Max Haring

    PhD student from 2003-2007. The Title of Max’s thesis is: Paramutation and chromatin dynamics in maize. Max defended his thesis Nov 12, 2008. He was paid by the University of Amsterdam.

     

    Former HLO, BSc & MSc Students

    Guy Koentjes, BSc student (internship), 2021

    Isabelle Tol, BSc student (internship), 2021

    Wessel Groot, MSc student (internship), 2021

    Thomas Rietbergen, MSc student (internship), 2021

    Kevin Peek, MSc student (internship), 2021

    Kees Buhrman, BSc student (internship), 2019

    Jessica Offeringa, BSc student (voluntary work), 2018

    Myrthe Praat, MSc student (internship), 2017

    Ahmad Husained, HLO student (internship), 2016-2017

    Pita de Kok, BSc student (internship), 2016

    Thalia Luden, BSc student (internship), 2016

    Roel Musch, HLO student (internship), 2015

    Aimee Walmsley, MSc student (internship), 2015

    Nigel Pearson, BSc student (internship), 2014

    Yara Grigoleit, MSc student (internship), 2014

    Mike Mensink, BSc student (internship), 2013

    Sjoerd Smit, MSc student (internship), 2013

    Alexander van Wieringen, BSc student (internship), 2012

    Guido Holstege, MSc student (internship), 2012

    Annemarie Castricum, HLO student (internship), 2011-2012

    Bas Jansen, MSc student (internship), 2011

    Pegah Poorfarai, MSc student (internship), 2009-2010

    Michael Ignarski, MSc student RWTH-Aachen University, Germany (internship), 2008-2009

    Gerben Marsman, MSc student (internship), 2008

    Mara de Sain, MSc student (internship), 2007-2008

    Elisa Teunissen, HLO student (internship), 2006

    Yan Yang, MSc student (internship), 2005

    Joke van Bemmel, MSc student (internship), 2004-2005

    Joke van Bemmel, BSc student (internship), 2003

     

     

    Guest Researchers

    Victor Sánchez Camargo, 2016, guest scientist for 5 months, learning ChIP

    Tomas Beseda, 2014, guest scientist for 2 weeks, getting acquainted with 3C

    Linlin Zheng, 2013, guest scientist for 2 weeks, learning ChIP

    Natalia Borowska,2012, guest scientist for 2 weeks, learning ChIP

    Just started as PI in the van Driel lab, winter 2002-2003
  • Publications

    2022

    • Martinho, C., Wang, Z., Ghigi, A., Buddle, S., Barbour, F., Yarur, A., Gouil, Q., Müller, S., Stam, M., Liu, C., & Baulcombe, D. C. (2022). CHROMOMETHYLTRANSFERASE3/KRYPTONITE maintains the sulfurea paramutation in Solanum lycopersicum. Proceedings of the National Academy of Sciences of the United States of America, 119(13), e2112240119. https://doi.org/10.1073/pnas.2112240119
    • Schmitz, R. J., Grotewold, E., & Stam, M. (2022). Cis-regulatory sequences in plants: Their importance, discovery, and future challenges. The Plant Cell, 34(2), 718-741. https://doi.org/10.1093/plcell/koab281

    2021

    2020

    • Sánchez-Camargo, V. A., Suárez-Espinoza, C., Romero-Rodríguez, S., Garza-Aguilar, S. M., Stam, M., García-Ramírez, E., Lara-Núñez, A., & Vázquez-Ramos, J. M. (2020). Maize E2F transcription factors. Expression, association to promoters of S-phase genes and interaction with the RBR1 protein in chromatin during seed germination. Plant Science, 296, [110491]. https://doi.org/10.1016/j.plantsci.2020.110491 [details]
    • Zisis, D., Krajewski, P., Stam, M., Weber, B., & Hövel, I. (2020). Analysis of 4C-seq data: A comparison of methods. Journal of bioinformatics and computational biology, 18(1), [2050001]. https://doi.org/10.1142/S0219720020500018 [details]

    2019

    2018

    • Chouaref, J., de Boer, E., Fransz, P., & Stam, M. (2018). Protocol for Chromatin Immunoprecipitation of Meiotic-Stage-Specific Tomato Anthers. Current protocols in plant biology, 3(3), [e20074]. https://doi.org/10.1002/cppb.20074 [details]
    • Lauss, K., Wardenaar, R., Oka, R., van Hulten, M. H. A., Guryev, V., Keurentjes, J. J. B., ... Johannes, F. (2018). Parental DNA methylation states are associated with heterosis in epigenetic hybrids. Plant Physiology, 176(2), 1627–1645. https://doi.org/10.1104/pp.17.01054 [details]
    • Tark-Dame, M., Weber, B., de Sain, M., Anggoro, D. T., Bader, R., Walmsley, A., ... Stam, M. (2018). Generating Transgenic Plants with Single-copy Insertions Using BIBAC-GW Binary Vector. Journal of Visualized Experiments, 133, [e57295]. https://doi.org/10.3791/57295 [details]
    • Weber, B., Jamge, S., & Stam, M. (2018). 3C in Maize and Arabidopsis. In M. Bemer, & C. Baroux (Eds.), Plant Chromatin Dynamics: Methods and Protocols (pp. 247-270). (Methods in Molecular Biology; Vol. 1675). New York: Humana Press. https://doi.org/10.1007/978-1-4939-7318-7_15 [details]
    • van Hulten, M. H. A., Paulo, M-J., Kruijer, W., Blankestijn-De Vries, H., Kemperman, B., Becker, F. F. M., ... Keurentjes, J. J. B. (2018). Assessment of heterosis in two Arabidopsis thaliana common-reference mapping populations. PLoS ONE, 13(10), [e0205564]. https://doi.org/10.1371/journal.pone.0205564 [details]

    2017

    2016

    2015

    2014

    • van Gent, J. I., Madzima, T. F., Bader, R., Kent, M. R., Zhang, X., Stam, M., ... Dawe, R. K. (2014). Accessible DNA and Relative Depletion of H3K9me2 at Maize Loci Undergoing RNA-Directed DNA Methylation. The Plant Cell, 26(12), 4903-4917. https://doi.org/10.1105/tpc.114.130427 [details]

    2013

    2012

    2010

    2009

    2007

    2005

    • Louwers, M. L. D., Haring, M., & Stam, M. (2005). When alleles meet: Paramutation. In P. Meyer (Ed.), Plant Epigenetics (pp. 134-173). Oxford, UK: Blackwell Publ. Ltd.. [details]
    • Stam, M., & Scheid, O. M. (2005). Paramutation: an encounter leaving a lasting impression. Trends in Plant Science, 10, 283-290. https://doi.org/10.1016/j.tplants.2005.04.009 [details]

    2004

    2002

    • Chandler, V. L., Stam, M., & Sidorenko, L. V. (2002). Long-distance cis and trans interactions mediate paramutation. Advances in Genetics Incorporating Molecular Genetic Medicine, 46, 215-234. [details]
    • Stam, M., Belele, C., Dorweiler, J. E., & Chandler, V. L. (2002). Differential chromatin structure within a tandem array 100 kb upstream of the maize b1 locus is associated with paramutation. Genes & Development, 16, 1906-1918. https://doi.org/10.1101/gad.1006702 [details]
    • Stam, M., Belele, C., Ramakrishna, W., Dorweiler, J. E., Bennetzen, J. L., & Chandler, V. L. (2002). The regulatory regions required for B' paramutation and expression are located far upstream of the maize b1 trascribed sequences. Genetics, 162, 917-930. [details]

    2000

    • Stam, M., Lavin, T., & Chandler, V. L. (2000). Npi402 and ncsu1 are identical; inra1 (tmp) maps upstream of the b promoter. Maize Genetics Coop Newsl., 74, 66-67. [details]
    • Stam, M., de Bruin, R., van Blokland, R., van der Hoorn, R. A. L., Mol, J. N. M., & Kooter, J. M. (2000). Distinct features of post-transcriptional gene silencing by antisense transgenes in single copy and inverted T-DNA repeat loci. Plant Journal, 21(1), 27-42. https://doi.org/10.1046/j.1365-313x.2000.00650.x [details]

    Talk / presentation

    • Stam, M. E. (invited speaker) (18-5-2016). Gene regulation by epigenetics and distant enhancers, European Maize Meeting in Hamburg , Hamburg .
    • Stam, M. E. (invited speaker) (4-5-2016). Gene regulation by epigenetics and distant enhancers, University of Cambridge, Cambridge CB2 1TN, UK.
    • Stam, M. E. (invited speaker) (16-3-2016). Gene regulation by epigenetics and distant enhancers, University of Georgia.
    • Stam, M. E. (speaker) (7-4-2011). Epigenetics for plant breeding managers, RijkZwaan, De Lier, the Netherlands.
    • Stam, M. E. (speaker) (25-3-2011). Gene regulation by epigenetics and chromosomal in cis and in trans interactions & implications for plant breeding, Monsanto multinational, the Netherlands.
    This list of publications is extracted from the UvA-Current Research Information System. Questions? Ask the library or the Pure staff of your faculty / institute. Log in to Pure to edit your publications. Log in to Personal Page Publication Selection tool to manage the visibility of your publications on this list.
  • Ancillary activities
    • No ancillary activities