A major unresolved challenge in biology is to decipher how cells can exist in the diverse cellular states that make up a functional organism while carrying the same genomic information. Transcription factors are responsible for the deposition of epigenomic modifications upon the genome that serve as instructions as to how the genome is being read in each different cell type, thus allowing the cell to adopt a specialized state. Furthermore, these instructions are highly dynamic and can change under the influence of extracellular cues presenting the cells with the ability to respond to changes in their environment.
Our goal is to understand the complexity of the epigenomic landscape and its role during development, and disease progression through large scale ChIP-sequencing analysis. We combine this with in vitro stem cell based assays and model organisms to use this large scale information in order to understand and control cell state changes.
About the research
Vermunt, M.W., Reinink, P., Korving J., de Bruijn, E., Creyghton, P.M., Basak, O., Geeven, G., Toonen, P.W., Lansu, N., Meunier, C., Heesch, S., Netherlands Brain Bank; Clevers, H., de Laat, W., Cuppen, E. and Creyghton M.P.. (2014) Large scale identification of co-regulated enhancer networks in the adult human brain. Cell Rep. 9: 1-13
Creyghton, M.P., Cheng, A., Welstead, G.G., Kooistra, T., Carey, B.W., Steine, E.J., Hanna, J., Lodato, M.A., Frampton ,G.M., Sharp, P.A., Boyer, L.A., Young, R.A., Jaenisch, R. (2010) Histone H3K27ac seperates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. 107: 21931-21936.
Hanna, J., Saha, K., Pando, B., van Zon, B., Lengner, C.J., Creyghton, M.P., van Oudenaarden, A., Jaenisch, R. (2009) Direct reprogramming is a stochastic process amenable to acceleration. Nature 462: 595-601.
Creyghton, M.P., Markoulaki, S., Levine, S., Hanna, J., Lodato, M.A., Sha, K., Young, R.A., Jaenisch, R., Boyer, L.A. (2008) H2AZ if enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 135: 649-661.
Hanna, J., Markoulaki, S., Schorderet, P., Carey, B.W., Beard, C., Wernig, M., Creyghton, M.P., Steine, E.J., Cassady, J.P., Foreman, R., Lengner, C.J., Dausman, J.A., Jaenisch, R. (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133: 250-264.