“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 in B cells undergoing pluripotent reprogramming.

Selected Publications

Liang Z, Brown KE, Carroll T, Taylor B, Vidal IF, Hendrich B, Rueda D, Fisher AG, Merkenschlager M. (2017). A high-resolution map of transcriptional repression. Elife. Mar 20;6. pii: e22767. doi: 10.7554/eLife.22767.

Van de Pette M, Abbas A, Feytout A, McNamara G, Bruno L, To WK, Dimond A, Sardini A, Webster Z, McGinty J, Paul EJ, Ungless MA, French PM, Withers DJ, Uren A, Ferguson-Smith AC, Merkenschlager M, John RM, Fisher AG.(2017) Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults. Cell Rep. Jan 31;18(5):1090-1099. doi: 10.1016/j.celrep.2017.01.010.

Cantone I, Dharmalingam G, Chan YW, Kohler AC, Lenhard B, Merkenschlager M, Fisher AG. (2017) Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation. Genome Biol. Jan 25;18(1):2. doi: 10.1186/s13059-016-1136-4.

Cantone, I., Bagci, H., Dormann, D., Dharmalingam, G., Nesterova, T., Brockdorff, N., Rougeulle, C., Vallot, C., Heard, E., Chaligne, R., Merkenschlager, M., Fisher, A.G., (2016). Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming, Nature Communications. 7:12354 doi: 10.1038/ncomms12354.

Landeira, D., Bagci, H., Malinowski, A.R., Brown, K.E., Soza-Ried, J., Feytout, A., Webster, Z., Ndjetehe, E., Cantone, I., Asenjo, H.G., Brockdorff, N., Carroll, T., Merkenschlager, M., Fisher, A.G. et al., (2015). Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development, Cell Reports, Vol: 12, Pages: 573-586, ISSN: 2211-1247.

Ing-Simmons, E., Seitan, V.C., Faure, A.J., Flicek, P., Carroll, T., Dekker, J., Fisher, A.G., Lenhard, B., Merkenschlager, M. (2015). Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin. Genome Research, 25 (4), 504-513. ISSN: 1088-9051.

Lavagnolli, T., Gupta, P., Hoermanseder, E., Mira-Bontenbal, H., Dharmalingam, G., Carroll, T., Gurdon, J.B., Fisher, A.G., Merkenschlager, M. (2015). Initiation and maintenance of pluripotency gene expression in the absence of cohesin. Genes & Development, 29, 23-38. ISSN: 0890-9369.

Blevins, R., Bruno, L., Carroll, T., Elliott, J., Marcais, A., Loh, C., Hertweck, A., Krek, A., Rajewsky, N., Chen, C.-Z., Fisher, A.G., Merkenschlager, M. (2015). microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes. PLOS Genetics, 11. ISSN: 1553-7390.

Marcais, A., Blevins, R., Graumann, J., Feytout, A., Dharmalingam, G., Carroll, T., Amado, I.F., Bruno, L., Lee, K., Walzer, T., Mann, M., Freitas, A.A., Boothby, M., Fisher, A.G., Merkenschlager, M. (2014). microRNA-mediated regulation of mTOR complex components facilitates discrimination between activation and anergy in CD4 T cells. Journal of Experimental Medicine, 211, 2281-2295. ISSN: 0022-1007.

Merkenschlager, M., Odom, D.T. (2013). CTCF and Cohesin: Linking Gene Regulatory Elements with Their Targets. CELL, 152 (6), 1285-1297. ISSN: 0092-8674.

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., Koseki, H., Merkenschlager, M., Fisher, A.G. (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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