“We use lymphocytes as models to study how gene expression patterns are transmitted through cell division, and to explore the molecular basis of lineage choice”

We study transcriptional and epigenetic mechanisms that underlie cellular differentiation and experimental reprogramming. Our core research activities include the following interrelated areas:

  • Pluripotency and reprogramming
  • Polycomb repressor complexes in stem cells
  • Cohesin function in gene expression and genome organisation
  • Ikaros family transcription factors

We combine classical cell biology and genetics approaches with current technologies to address the events involved in maintaining embryonic stem (ES) cell pluripotency versus differentiation towards mesoderm, endoderm and ectoderm, as well as the mechanisms of T and B cell lineage choice and differentiation.

Lymphocyte Development

DNA synthesis (green) in B cells undergoing pluripotent reprogramming.

Selected Publications

Seitan, V. C., Faure, A. J., Zhan, Y., Patton, R., Lajoie, B. R., Ing-Simmons, E., Lenhard, B., Giorgetti, L., Heard, E., Fisher, A. G., Flicek, P., Dekker, J., Merkenschlager, M. (2013). Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Genome Research, 23 (12), 2066–2077.

Piccolo, F. M., Bagci, H., Brown, K. E., Landeira, D., Soza-Ried, J., Feytout, A., Mooijman, D., Hajkova, P., Leitch, H. G., Tada, T., Kriaucionis, S., Dawlaty, M. M., Jaenisch, R., Merkenschlager, M., Fisher, A. G. (2013). Different roles for tet1 and tet2 proteins in reprogramming-mediated erasure of imprints induced by EGC fusion. Molecular Cell, 49 (6), 1023–1033.

Tsubouchi, T., Soza-Ried, J., Brown, K., Piccolo, F. M., Cantone, I., Landeira, D., Bagci, H., Hochegger, H., Merkenschlager, M., Fisher, A. G., (2013). DNA synthesis is required for reprogramming mediated by stem cell fusion. Cell, 152 (4), 873–883.

Seitan, V. C., Hao, B., Tachibana-Konwalski, K., Lavagnolli, T., Mira-Bontenbal, H., Brown, K. E., Teng, G., Carroll, T., Terry, A., Horan, K., Marks, H., Adams, D. J., Schatz, D. G., Aragon, L., Fisher, A. G., Krangel, M. S., Nasmyth, K., Merkenschlager, M. (2011). A role for cohesin in t-cell-receptor rearrangement and thymocyte differentiation. Nature, 476 (7361), 467–471.

Jørgensen, H. F., Fisher, A. G. (2010). Can controversies be put to REST? Nature, 467 (7311).

Landeira, D., Sauer, S., Poot, R., Dvorkina, M., Mazzarella, L., Jørgensen, H. F., Pereira, F. F., Leleu, M., Piccolo, F. M., Spivakov, M., Brookes, E., Pombo, A., Fisher, C., Skarnes, W. C., Snoek, T., Bezstarosti, K., Demmers, J., Klose, R. J., Casanova, M., Tavares, L., Brockdorff, N., Merkenschlager, M., Fisher, A. G. (2010). Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA polymerase II to developmental regulators. Nature Cell Biology, 12 (6), 618–624.

Pereira, C. F., Piccolo, F. M., Tsubouchi, T., Sauer, S., Ryan, N. K., Bruno, L., Landeira, D., Santos, J., Banito, A., Gil, J., (2010). ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency. Cell Stem Cell, 6 (6), 547–556.

Hadjur, S., Williams, L. M., Ryan, N. K., Cobb, B. S., Sexton, T., Fraser, P., Fisher, A. G., Merkenschlager, M. (2009). Cohesins form chromosomal cis-interactions at the developmentally regulated IFNG locus. Nature, 460 (7253), 410–413.

Parelho, V., Hadjur, S., Spivakov, M., Leleu, M., Sauer, S., Gregson, H. C., Jarmuz, A., Canzonetta, C., Webster, Z., Nesterova, T., Cobb, B. S., Yokomori, K., Dillon, N., Aragon, L., Fisher, A. G., Merkenschlager, M. (2008). Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell, 132 (3), 422–433.

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