Swammerdam Institute for Life Sciences

Research line Dr. M.E. (Maike) Stam

Gene regulation by epigenetics and chromosomal interactions

The Stam subgroup studies the role of epigenetic mechanisms and chromosomal interactions in gene regulation and in targeted mutagenesis using plants as a model system. Both Epigenetic gene regulation and chromosomal interactions are essential for normal growth and development. Epigenetic gene regulation refers to mitotically or meiotically heritable changes in gene expression that do not involve DNA sequence changes, but changes in DNA methylation and chromatin structure instead. Recent studies have shown that, besides gene control by nearby cis-acting regulatory elements, gene regulation in higher eukaryotes also involves physical interactions between chromosomal regions up to hundreds of kilobase pairs apart on the same chromosome (cis), or between regions located on different chromosomes (trans).

In the context of epigenetics and chromosomal interactions different studies are being performed:

 

1) Unraveling the mechanisms underlying paramutation at the maize B-I and B’ alleles.

B’ and B-I have the same DNA sequence, but differ in DNA methylation and chromatin structure and are therefore called epialleles. The expression of the b1 gene is controlled by regulatory sequences up to at least 110 kb upstream, and the low-expressing B’ epiallele communicates in trans with the high-expressing B-I epiallele, changing B-I into B’ in a mitotically and meiotically heritable manner in a process called paramutation. Rechien Bader (research technician) investigates the epigenetic mechanisms underlying this process.

 

2) Quantitative relationships between chromatin looping and gene activity.

The functional relationship between gene activity and long-distance chromosomal interactions is investigated using Arabidopsis thaliana as a model organism. This study is a collaboration with Dr. Paul Fransz (NOG) and employs Chromatin Conformation Capture technology and 3D-FISH. Mathematical modeling will be used to establish quantitative relationships between chromatin folding and gene activity (collaboration with Prof. D. Heermann, Heidelberg). Iris Hövel (PhD student) is appointed on this project.

 

3) The role of epigenetic regulation and chromosomal interactions in hybrid vigour.

The aim of this project, which is performed in collaboration with the groups of Prof. Angenent, Dr. Keurentjes and Dr Sanchez Perez at Wageningen University, is to enhance the understanding of the role of epigenetic mechanisms and chromosomal interactions in hybrid vigour, which has been a major innovation improving the yield of food crops. To further improve yield, it is essential to understand the mechanisms underlying hybrid vigour. Recent data obtained by other groups indicate a role for epigenetic regulation in hybrid vigour. Kathrin Lauss (PhD student) is appointed on this project.

 

4) Epigenetics meets targeted mutagenesis.

To meet the global food challenge, plant breeders are continuously searching for new sources of genetic variation and are consequently interested in novel technologies for precise genome engineering, e.g. oligonucleotide-directed mutagenesis (ODM). Such technologies allow the introduction of small, targeted modifications, but are hampered by low efficiencies. This 4-year project, funded by STW and industrial partners, aims at identifying epigenetic drugs and/or mutations that significantly enhance the efficiency of ODM. Arabidopsis will be used as model system; promising results will be evaluated in tomato. The project will be performed by Mariliis Tark-Dame (Post-doc) and Damar Anggoro (technician), in close collaboration with Dr. Michiel de Both and Dr. Franck Lhuissier of KeyGene (Wageningen), and with four international seed companies.

 

5) Epigenetic regulation of economically important plant traits. See: EpiTRAITS

Maike Stam is coordinator of the EU FP7 Marie Curie ITN EpiTRAITS (12 full partners, 3 associated partners; 11 PhD and 3 Post-doc positions, start date October 2012). The mission of EpiTRAITS is to train young researchers in epigenetic gene regulation and flowering in the model plant Arabidopsis thaliana and the crop plants maize (Zea mays) and barley (Hordeum vulgare). EpiTRAITS will focus on one of the key plant traits, flowering, which is controlled by various epigenetic mechanisms. The scientific program aims to bridge the gap between fundamental and applied research by translating results from epigenetic research in model organisms to improved technologies for crop breeding and molecular diagnostic tools. In the Stam group, Blaise Weber and Rurika Oka (PhD students) are appointed on this project.

 

6) The control of meiotic recombination.

Crop improvement by classical breeding involves the introgression of new traits, e.g. resistance to pathogens or tolerance to changed climate conditions, from wild species into cultivated crops. One of the major obstacles to accomplish this is the low transmission rate of the desired combination of traits. This is due to limitations in homeologous recombination during meiosis. Two projects in the Fransz-Stam group focus on meiotic recombinants. A partnership STW – Rijk Zwaan project aims to identify (novel) genes that control homeologous recombination in tomato. Esther de Boer (Post-doc) is appointed to this project. The other project is the Marie Curie ITN COMREC - Control of meiotic recombination: from Arabidopsis to crops – in which the Fransz-Stam group participates. The ITN has 11 full partners and includes several companies as associated partners. Jihed Chouaref (PhD student) is appointed to the COMREC project.

 

2 February 2015