Epigenomics research

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 these analyses with stem cell based assays and model organisms to understand the cell state changes that underly developent and evolution of the human brain and its susceptibility to diseases including cancer.

Menno Creyghton

Menno Creyghton received his PhD in 2006 at the University of Utrecht for his work at the Netherlands Cancer Institute in the laboratory of Prof. Rene Bernards where he worked on functional genetic screens to identify genes in cancer relevant pathways using RNAi. He received a fellowship from the Dutch Cancer Society and joined the lab of Prof. Rudolf Jaenisch at the Whitehead institute for biomedical research at the Massachusetts Institute of Technology (Cambridge, MA, USA) where he studied the process of reprogramming adult cells into a stem cell like fate. He focused on the massive epigenomic changes that occur during cell fate determination using large scale epigenomic profiling. In 2011 he started his laboratory at the Hubrecht Institute where he uses these technologies to study the epigenome during development and disease in human tissue.

Team membersCreyghton

Menno Creyghton

Group Leader
m.creyghton [at] hubrecht.eu

Sander Tan

PhD-student
s.tan@hubrecht.eu

Caroline Wiggers

PhD-student
c.wiggers@hubrecht.eu

Maartje Vermunt

PhD student
m.vermunt@hubrecht.eu

Bas Castelijns

PhD student
b.castelijns@hubrecht.eu

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Research

Creyghton: Epigenomics

Our laboratory uses genome scale sequencing techniques to analyze the epigenetic instructions that determine how the genome is being interpreted by the cell. In particular we analyze how these instructions contributed to the development and evolution of the human brain and the emergence of neurological disorders. Furthermore we study how cancer evolves in patient tissue. We use a combination of computational analyses, cell based assays and transgenic animals to achieve these goals.

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Key publications

Vermunt, M.W., Tan S.C., Castelijns B., Geeven, G., Reinink, P., de Bruijn, E., Kondova I., Persengiev S., Netherlands Brain Bank; Bontrop R., Cuppen, E., de Laat, W. and Creyghton M.P. Epigenomic annotation of gene regulatory alterations during evolution of the primate brain. Nature Neurosci. (2016) 3: 494-503 pdf

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. Large scale identification of co-regulated enhancer networks in the adult human brain. Cell Rep. (2014) 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. (2010) 107: 21931-21936.

Creyghton, M.P., Markoulaki, S., Levine, S., Hanna, J., Lodato, M.A., Sha, K., Young, R.A., Jaenisch, R., Boyer, L.A. H2AZ if enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell (2008) 135: 649-661.

All publications

Vermunt, M.W., Tan S.C., Castelijns B., Geeven, G., Reinink, P., de Bruijn, E., Kondova I., Persengiev S., Netherlands Brain Bank; Bontrop R., Cuppen, E., de Laat, W. and Creyghton M.P. Epigenomic annotation of gene regulatory alterations during evolution of the primate brain. Nature Neurosci. (2016) 3: 494-503 pdf

Geeven G., Zhu Y., Kim B.J., Bartholdy B.A., Yang S.M., Macfarlan T.S., Gifford W.D., Pfaff S.L., Verstegen M.J., Pinto H., Vermunt M.W., Creyghton M.P., Wijchers P.J., Stamatoyannopoulos J.A., Skoultchi A.I., de Laat W. Local compartment changes and regulatory landscape alterations in histone H1-depleted cells. Genome Biol. (2015) Dec 23;16(1):289

Peeters J.G., Vervoort S.J., Tan S.C., Mijnheer G., de Roock S., Vastert S.J., Nieuwenhuis E.E., van Wijk F., Prakken B.J., Creyghton M.P., Coffer P.J., Mokry M., van Loosdregt J. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression. Cell Rep. (2015) Sep 29;12(12):1986-96.

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. (2014) 9: 1-13

Kanski, R., Sneeboer, M., van Bodegraven, E., Sluijs, J.A., Kropff, W.W., Vermunt, M.W., Creyghton, M.P., De Filippis, L., Vescovi, A., Aronica, E., van Tijn, P., van Strien, M and Hol, E. Histone acethylation in astrocytes supresses GFAP and stimulates a re-organization of the intermediate filament network. J. Cell Sci. (2014) Oct 15;127(Pt 20):4368-80

Welstead G.G., Creyghton, M.P., Bilodeau S., Cheng A.W., Markoulaki S., Young R.A., Jaenisch R. X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc. Natl. Acad. Sci. USA. (2012) Aug 7; 109(32):13004-9.

Carey B.W., Markoulaki S., Hanna, J., Faddah D.A., Buganim Y, Kim J, Ganz K, Steine E.J., Cassady J.P., Creyghton, M.P., Welstead G.G., Gao Q, Jaenisch R. Reprogramming factor stoichiometry influences the epigenetic state and biological properties of induced pluripotent stem cells. Cell Stem Cell. (2011) Dec 2; 9(6):588-98.

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. Histone H3K27ac seperates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. (2010) 107: 21931-21936.

Hanna, J., Saha, K., Pando, B., van Zon, B., Lengner, C.J., Creyghton, M.P., van Oudenaarden, A., Jaenisch, R. Direct reprogramming is a stochastic process amenable to acceleration. Nature (2009) 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. H2AZ if enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell (2008) 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. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell (2008) 133, 250-264.

Eichhorn P.J., Creyghton, M.P., Bernards R. Protein phosphatase 2A regulatory subunits and cancer. BBA reviews on cancer. (2008) 1795, 1-15

Eichhorn P.J., Creyghton, M.P., Wilhelmsen K., van Dam H., Bernards R. A RNA interference screen identifies the Protein Phosphatase 2A subunit PR55gamma as a stress-sensitive inhibitor of c-SRC. PloS Genet. (2007) Dec;3(12):e218.

Creyghton, M.P., Roël G, Eichhorn P.J., Vredeveld L.C., Destrée O., Bernards R. PR130 is a modulator of the Wnt-signaling cascade that counters repression of the antagonist Naked cuticle. Proc. Natl. Acad. Sci. USA. (2006) Apr 4; 103(14):5397-402

Creyghton, M.P., Roël G, Eichhorn P.J., Hijmans E.M., Maurer I., Destrée O., Bernards R. PR72, a novel regulator of Wnt signaling is required for Naked cuticle function. Genes Dev. (2005) 19(3): 376-86.