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Creyghton group

Epigenetics and stem cell development

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.

Cell identity is determined by developmental programs that use select transcription factors that impose an epigenetic signature upon the genome thus enforcing select gene expression programs. These signatures can often be found deregulated in developmental abnormalities and later onset complex disease.

Our goal is to understand the complexity of the epigenetic 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 control cell state changes.

About the research

Key publications
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.

Creyghton, M.P., Roël, G., Eichhorn, P.J., Vredeveld, L.C., Destrée, O., Bernards, R.  (2006) PR130 is a modulator of the Wnt-signaling cascade that counters repression of the antagonist  Naked cuticle.  Proc. Natl. Acad. Sci.. 103: 5397-5402.

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