Can we train our genes?

Scientific Meeting Genootschap

On Thursday 18 January 2018 you are welcome at the Scientific Meeting of the Genootschap. The theme of the meeting is “How flexible is the epigenetic composition of our genome: Can we train our genes …? “

Datum18 januari 2018
Tijd18:00 – 20:00


  • dr. Pernette Verschure (SILS, UvA)
    Dynamic epigenetic regulation: Single cells can make the difference
  • prof.dr. Marianne Rots (UMCG)
    Epigenetic Editing: a one-and-done approach to realize the curable genome concept?

Programme and location

You are welcome from 17.30h for coffee, tea, and sandwiches. The lectures will start at 18.00h and end around 19.30h. After the lectures drinks will be served.

The location is Auditorium Sanquin, Plesmanlaan 125, 1066 CX Amsterdam. Sanquin has ample parking facilities. To use these, please contact the reception of Sanquin and indicate that you are attending the scientific meeting.

Directions to Sanquin

Target group

The meeting is open for members of the Genootschap, employees and PhD-students from AMC, FNWI, and ACTA of the University of Amsterdam and employees and PhD-students from FALW, FEW and VUMC of the Free University Amsterdam.


We would like to ask you to register for this meeting via


Epigenetic Editing: a one-and-done approach to realize the curable genome concept?

Marianne G Rots (

Professor of Molecular Epigenetics,  Department of Pathology & Medical biology, University Medical Center Groningen, the Netherlands (

Many diseases are associated with abnormal gene activity profiles. Epigenetic mechanisms, including DNA methylation and post-translational histone modifications, regulate gene activity in a stable, yet reversible manner. As such, epigenetics might play a crucial role in the development of various diseases. Importantly, as epigenetic marks are reversible, insights in abnormal epigenetic landscapes offer novel therapeutic potentials to alleviate or even cure deficits. Current epigenetic therapies are already used for cancer and epilepsy, and the recent CRISPR-revolution might provide possibilities for other diseases as well. CRISPR-Cas is based on designing RNA molecules to guide a nuclease (Cas9) to its target DNA site. Upon mutation of the nuclease activity (dCas), dCas can be fused to transcription regulatory proteins. Such Artificial Transcription Factors (ATFs) can restore gene activity of any gene at will, but the effects are presumed to be transient. We aim to induce sustained gene activity modulation by rewriting epigenetic marks at the locus of interest (Epigenetic Editing).

A major disadvantage of current epigenetic therapies include their genome-wide effects. To modulate the activity of a particular gene, ATFs or epigenetic regulatory proteins can be engineered to either repress or induce gene activity. To specifically, and sustainably, re-activate or silence dysregulated genes, we locally rewrite the epigenetic signature of these genes. Data from my laboratory, as well as from others, have demonstrated that rewritten epigenetic marks do result in gene activity changes2,3 and slowly we begin to understand how to achieve sustained transcription reprogramming4 As such, Epigenetic Editing aims to fulfill the promise of realizing the curable genome concept.


1de Groote ML et al. Nucleic Acids Res. (2012).

2Falahi F et al. Mol Cancer Res. (2013).

3Chen H et al. Nucleic Acid Res. (2014).  

4Cano-Rodriguez et al Nature Comm. (2016).

Dynamic epigenetic regulation: Single cells can make the difference

Pernette J. Verschure

Associate professor and Coordinator EU H2020 Marie Skłodowska-Curie ITN EpiPredict consortium (, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands (

All cells of one individual contain the same genetic material. But how do cells acquire cell identity and keep memory of their tissue origin? Our epigenome is essential in orchestrating the level and timing of its thousands of genes. Epigenetic marks include chemical modifications on DNA and connected histone proteins. These epigenetic signatures are associated with folding of the genome providing a guide for gene activity. Epigenetic patterning is crucial for ‘healthy’ cell and tissue performance. Epigenetic alterations occur when we age and increase the likelihood to develop diseases, the long-term impact for instance diet, exercise, tobacco and environmental pollutants.

How dynamic epigenetic interactions emerge in single cells and how they contribute to biological functionality is still largely unresolved. Single-cell technologies noted that identical cells in a population have inherently variable gene activity levels impacting cell survival under fluctuating conditions. Research from my group, and also from others, illustrates that the use of epigenetically engineered mammalian cells and dedicated experimental and computational tools to modulate the epigenetic composition, are extremely powerful to interpret such epigenetics-related dynamics and heterogeneity.1,2,3.

Epigenetic dynamics is expected to play a crucial role in the development of pathological conditions for example as driver of breast cancer progression after treatment. Estrogen receptor positive (ER+) breast cancer cells are strikingly heterogeneous and upon endocrine treatment defined resistant cell subpopulations are detected. We put forward that cell-to-cell variability in epigenetic regulation allows particular cell types to escape from treatment taking transcriptional bursting into account4. This single cell approach, pinpointing the role of epigenetic plasticity in pathological conditions, opens an unexplored exciting field of research with great potential for individualized medicine.


1Anink-Groenen LC et al. (2014). Mechanistic stochastic model of histone modification pattern formation, Epigenetics Chromatin, 7: 30.

2Wijchers PJ et al. (2016). Cause and consequence of tethering a subTAD to different nuclear compartments. Mol Cell, 61: 461.

3 Kempe H et al. (2015). The volumes and transcript counts of single cells reveal concentration homeostasis and capture biological noise. Mol Biol Cell, 26: 797.

4Magnani L et al. (2017): Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ERα metastatic breast cancer Nat Genet 49:444.