Matthias Merkenschlager
Group Members
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Funding
“We explore gene regulatory mechanisms that drive mammalian cell type specification.”
We study the relationship between 3D genome organisation and gene expression, based on our discovery that cohesin associates with CTCF to form chromatin loops that affect transcription.
Cohesin associates with CTCF to form chromatin loops that affect transcription.
3D gene control is a fundamental biological mechanism, and relevant to understanding cohesin mutations in human development and cancer.
Cohesin mutations compromise inflammatory gene expression in experimental systems and in human disease.
Cuartero et al., Nat Immunology 19: 932-41, 2018
We are interested in disease-related transcription factors, including the Runx and Ikaros families.
Evolutionary reconstruction of Runx transcription factor sequences and functional impact on gene regulation.
Bruno et al., Nat Immunology 20: 1372-80, 2019
Selected Publications
Buenaventura T, Bagci H, Patrascan I, Graham JJ, Hipwell KD, Oldenkamp R, King JWD, Urtasun J, Young G, Mouzo D, Gomez-Cabrero D, Rowland BD, Panne D, Fisher AG, Merkenschlager M. 2024. Competition shapes the landscape of X-chromosome-linked genetic diversity. Nat. Genetics 56: 1678-88
Al-Jibury E, King JWD, Guo Y, Lenhard B, Fisher AG, Merkenschlager M, Rueckert D. 2023 A deep learning method for replicate-based analysis of chromosome conformation contacts using Siamese neural networks. Nat Commun 14: 5007. doi: 10.1038/s41467-023-40547-9.
Guo Y, Al-Jibury E, Garcia-Millan R, Ntagiantas K, King JWD, Nash AJ, Galjart N, Lenhard B, Ruecekert D, Fisher AG, Pruessner G, Merkenschlager M. (2022). Chromatin jets define properties of cohesin-driven in vivo loop extrusion. Molecular Cell 82, 1-12
Robles-Rebollo I, Cuartero S, Canellas A, Wells S, Karimi MM, Mereu E, Chivu AG, Heyn H, Whilding C, Dormann D, Marguerat S, Rioja I, Prinjha RK, Stumpf MPH, Fisher AG, Merkenschlager M. (2022). Cohesin couples transcriptional bursting probabilities of inducible enhancers and promoters. Nature Communications 13: 4342 https://doi.org/10.1038/s41467-022-31192-9
Dsouza KB, Maslova A, Al-Jibury E, Merkenschlager M, Bhargava VK, Libbrecht MW. (2022). Learning representations of chromatin contacts using a recurrent neural network identifies genomic drivers of conformation. Nature Communications 13: 3704 https://doi.org/10.1038/s41467-022-31337-w
Calderon L, Weiss FD, Beagan JA, Oliveira MA, Georgieva R, Wang YF, Carroll T, Dharmalingam G, Gong W, Tossell K, de Paola V, Whilding C, Ungless MA, Fisher AG, Phillips-Cremins JE, Merkenschlager M. (2022). Cohesin-dependence of neuronal gene expression relates to chromatin loop length. eLife 11: e76539 https://doi.org/10.7554/eLife.76539
Karimi MM, Guo Y, Cui X, Pallikonda HA, Horková V, Wang Y-F, Ruiz Gil S, Rodriguez-Esteban G, Robles-Rebollo I, Bruno L, Georgieva R, Patel B, Elliott J, Dore MH, Dauphars D, Krangel MS, Lenhard B, Heyn H, Fisher AG, Štěpánek O, Merkenschlager M. (2021). The order and logic of CD4 CD8 lineage choice and differentiation in mouse thymus. Nature Communications 12: 99. https://doi.org/10.1038/s41467-020-20306-w
Weiss FD, Calderon L, Wang YF, Georgieva R, Guo Y, Cvetesic N, Kaur M, Dharmalingam G, Krantz ID, Lenhard B, Fisher AG, Merkenschlager M. 2021. Neuronal genes deregulated in Cornelia de Lange Syndrome respond to removal and re-expression of cohesin. Nature Communications 12: 2919 https://doi.org/10.1038/s41467-021-23141-9
Djeghloul D, Patel B, Kramer H, Dimond A, Whilding C, Brown K, Kohler A, Feytout A, Veland N, Elliott J, Bharat TAM, Tarafder AK, Löwe J, Ng BL, Guo Y, Guy J, Huseyin MK, Klose RJ, Merkenschlager M, Fisher AG. (2020). Identifying proteins bound to native mitotic ESC chromosomes reveals chromatin repressors are important for compaction. Nature Communications, 11, 4118.
Van de Pette M, Galvao A, Millership SJ, To W, Dimond A, Prodani C, McNamara G, Bruno L, Sardini A, Webster Z, McGinty J, French P, Uren AG, Castillo-Fernandez J, John RM, Ferguson-Smith AC, Merkenschlager M, Kelsey G, Fisher AG. (2020). Epigenetic change induced by in utero dietary challenge provokes phenotypic variability across multiple generations of mice. bioRxiv, https://doi.org/10.1101/2020.08.07.241034
Bruno L, Ramlall V, Studer RA, Sauer S, Bradley D, Dharmalingam G, Carroll T, Ghoneim M, Chopin M, Nutt SL, Elderkin S, Rueda DS, Fisher AG, Siggers T, Beltrao P, Merkenschlager M. (2019). Selective deployment of transcription factor paralogs with submaximal strength facilitates gene regulation in the immune system. Nature Immunology, https://doi.org/10.1038/s41590-019-0471-5
Ferreirós-Vidal I, Carroll T, Zhang T, Lagani V, Ramirez RN, Ing-Simmons E, Gómez-Valadés AG, Cooper L, Liang Z, Papoutsoglou G, Dharmalingam G, Guo Y, Tarazona S, Fernandes SJ, Noori P, Silberberg G, Fisher AG, Tsamardinos I, Mortazavi A, Lenhard B, Conesa A, Tegner J, Merkenschlager M, Gomez-Cabrero D. (2019). Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation. PLoS Biology, 12; 17(4).
Cuartero S, Weiss FD, Dharmalingam G, Guo Y, Ing-Simmons E, Masella S, Irene Robles-Rebollo, Xiao X, Wang Y-F, Barozzi I, Djeghloul D, Amano MT, Niskanen H, Petretto E, Dowell RD, Tachibana K, Kaikkonen MU, Nasmyth KA, Lenhard B, Natoli G, Fisher AG, Merkenschlager M. (2018). Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation. Nature Immunology 19, 932–941.
Liang Z, Brown KE, Carroll T, Taylor B, Ferreiros Vidal I, Hendrich B, Rueda D, Fisher AG, Merkenschlager M. (2017). A high-resolution map of transcriptional repression. eLife 6, ISSN:2050-084X. 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 PMW, 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 Reports 18(5):1090-1099. DOI: http://dx.doi.org/10.1016/j.celrep.2017.01.010.
Fisher AG, Stumpf MPH, Merkenschlager M. (2017). Reconciling Epigenetic Memory and Transcriptional Responsiveness. Cell Systems 4(4):373-374. doi: 10.1016/j.cels.2017.04.005. PMID: 28448796.
Merkenschlager M, Nora EP. (2016). CTCF and Cohesin in Genome Folding and Transcriptional Gene Regulation. Annual Review of Genomics and Human Genetics 17: 17-43, ISSN: 1527-8204.
Ing-Simmons E, Seitan VC, Faure AJ, Flicek P, Carroll T, Dekker J, Fisher AG, 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, Hörmanseder E, Mira-Bontenbal H, Dharmalingam G, Carroll T, Gurdon JB, Fisher AG, 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 CZ, Fisher AG, 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 IF, Bruno L, Lee K, Walzer T, Mann M, Freitas AA, Boothby M, Fisher AG, 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 DT. (2013). CTCF and Cohesin: Linking Gene Regulatory Elements with Their Targets Cell 152 (6), 1285-1297. ISSN: 0092-8674.
Seitan VC, Faure AJ, Zhan Y, McCord RP, Lajoie BR, Ing-Simmons E, Lenhard B, Giorgetti L, Heard E, Fisher AG, 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 FM, Bagci H, Brown KE, Landeira D, Soza-Ried J, Feytout A, Mooijman D, Hajkova P, Leitch HG, Tada T, Kriaucionis S, Dawlaty MM, Jaenisch R, Merkenschlager M, Fisher AG. (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 FM, Cantone I, Landeira D, Bagci H, Hochegger H, Merkenschlager M, Fisher AG. (2013). DNA synthesis is required for reprogramming mediated by stem cell fusion. Cell 152 (4), 873–883.
Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H, Brown KE, Teng G, Carroll T, Terry A, Horan K, Marks H, Adams DJ, Schatz DG, Aragon L, Fisher AG, Krangel MS, Nasmyth K, Merkenschlager M. (2011). A role for cohesin in t-cell-receptor rearrangement and thymocyte differentiation. Nature 476 (7361), 467–471.
Hadjur S, Williams LM, Ryan NK, Cobb BS, Sexton T, Fraser P, Fisher AG, 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 HC, Jarmuz A, Canzonetta C, Webster Z, Nesterova T, Cobb BS, Yokomori K, Dillon N, Aragon L, Fisher AG, Merkenschlager M. (2008). Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell 132 (3), 422–433.
