Dr. Jonathan H. Dennis
Ph.D., University College London, 2001; Postdoctoral, Massachusetts General Hospital
Graduate Faculty Status
Research and Professional Interests:
How can more than two meters of human genomic DNA be packed as chromatin into a five micrometer nucleus whose protein concentration approaches that of a protein crystal? I devoted my post-doctoral work to the development of techniques to describe the accessibility and organization of chromatin in the human nucleus, and I have used these technologies to study the biology of chromatin involved in the innate immune response. The long-term goal of my research is to apply and develop state-of-the-art techniques to large-scale detailed analysis of chromatin structure, thereby revealing the relationship between the regulation of chromatin architecture and cellular processes and clarifying the role of chromatin structure in the origin and mechanisms of disease.
A prevailing view of chromatin structure predicts that nucleosome distribution plays a role in gene regulation, and that nucleosome distribution will exhibit marked differences in disparate cell types with different gene expression programs. However, multiple studies have observed that nucleosome occupancy profiles are largely similar among disparate cell types with different gene expression programs, raising questions about the role of in-vivo nucleosome distribution on genome regulation. We have mapped nucleosome distribution at high temporal resolution during multiple genomic responses and have demonstrated that nucleosome repositioning is widespread, transient, genetically-encoded, and may potentiate regulatory factor binding. Additionally, we have shown that although basal nucleosome positions are highly similar between disparate cell types, the sensitivity of many nucleosomes to nuclease digestion varies greatly. These discoveries have allowed us to propose a hierarchical model for gene regulation that reconciles decades of chromatin research.Selected Publications:
Lei, I., West, J., Yan, Z., Gao, X., Fang, P., Dennis, J. H., Gnatovskiy, L., Wang, W., Kingston, R. E., Wang, Z. 2015. BAF250a regulates nucleosome occupancy and histone modifications in priming embryonic stem cell differentiation. J Biol Chem. 2015 Jun 12. pii: jbc.M115.637389. PMID: 26070559.
Fincher, J. A., Tyson, G. S., Dennis, J. H. 2015. DNA-Encoded Chromatin Structural Intron Boundary Signals Identify Conserved Genes with Common Function. Int J Genomics. 2015:167578. doi: 10.1155/2015/167578. PMID: 25861617.
Pope, B. D., Ryba, T., Dileep, V., Yue, F., Wu, W., Denas, O., Vera, D. L., Wang, Y., Hansen, R. S., Canfield, T. K., Thurman, R. E., Cheng, Y., Gülsoy, G., Dennis, J. H., Snyder, M. P., Stamatoyannopoulos, J. A., Taylor, J., Hardison, R. C., Kahveci, T., Ren, B., Gilbert, D. M. 2014. Topologically associating domains are stable units of replication-timing regulation. Nature. Nov 20;515(7527):402-5. doi: 10.1038/nature13986. PMID: 25409831.
Vera, D. L., Madzima, T. F., Labonne, J. D., Alam, M. P., Hoffman, G. G., Girimurugan, S. B., Zhang, J., McGinnis, K. M., Dennis, J. H., Bass, H. W. 2014. Differential nuclease sensitivity profiling of chromatin reveals biochemical footprints coupled to gene expression and functional DNA elements in maize. Plant Cell. 2014 Oct;26(10):3883-93. doi: 10.1105/tpc.114.130609. PMID: 25361955.
Sexton, B. S., Druliner, B. R., Avey, D., Zhu, F., Dennis, J. H. 2014. Changes in nucleosome occupancy occur in a chromosome specific manner. Genomics Data. 16 June 2014, DOI: 10.1016/j.gdata.2014.06.006.
Sexton, B. S., Avey, D., Druliner, B. R., Fincher, J. A., Vera, D. L., Grau, D. J., Borowsky, M. L., Gupta, S., Girimurugan, S. B., Chicken, E., Zhang, J., Noble, W. S., Zhu, F., Kingston, R. E., & Dennis, J. H. 2014. The spring-loaded genome: Nucleosome redistributions are widespread, transient, and DNA-directed. Genome Research, 24: 251-259.
Druliner, B. R., Fincher, J. A., Sexton, B. S., Vera, D. L., Roche, M., Lyle, S., & Dennis, J. H. 2013. Chromatin patterns associated with lung adenocarcinoma progression. Cell Cycle, 12(10), 1536-43.
Takebayashi, S., Dileep, V., Ryba, T., Dennis, J. H., & Gilbert, D. M. 2012. Chromatin-interaction compartment switch at developmentally regulated chromosomal domains reveals an unusual principle of chromatin folding. Proc Natl Acad Sci U S A, 109(31), 12574-9.
Fincher, J. A., and J. H. Dennis. 2011. DNA sequence contribution to nucleosome distribution. Pages 133-142 in J. Craig and N. Wong, eds., Epigenetics: A Reference Manual. Horizon Scientific Press, Norwich, U.K.
Spetman, B., S. Lueking, B. Roberts, and J. H. Dennis. 2011. Microarray mapping of nucleosome position. Pages in J. Craig and N. Wong, eds., Epigenetics: A Reference Manual. Horizon Scientific Press, Norwich, U.K.
Lubelsky, Y., T. Sasaki, M. A. Kuipers, I. Lucas, M. M. Le Beau, S. Carignon, M. Debatisse, J. A. Prinz, J. H. Dennis, and D. M. Gilbert. 2010. Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone. Nucleic Acids Research 38:3141-3155. doi: 10.1093/nar/gkq1276.
Fincher, J. A., and J. H. Dennis. 2010. A computational exploration of gene regulation by nucleosome position. Proceedings of ACM International Conference on Bioinformatics and Computational Biology, 386-389. doi: 10.1145/1854776.1854836.
Zhang, Y., X. Liu, J. A. Fincher, and J. H. Dennis. 2010. DNA sequence feature selection for intrinsic nucleosome positioning signals using AdaBoost. Proceedings of ACM International Conference on Bioinformatics and Computational Biology, 469-471. doi: 10.1145/1854776.1854860.
Gupta, S., J. H. Dennis, R. E. Thurman, R. E. Kingston, J. A. Stamatoyannopoulos, and W. S. Noble. 2008. Predicting human nucleosome occupancy from primary sequence. PLoS Computational Biology 4(8):e1000134.
Dennis, J. H., H.-Y. Fan, S. Reynolds, G. Yuan, J. G. Meldrim, D. J. Richter, D. G. Peterson, O. J. Rando, W. S. Noble, and R. E. Kingston. 2007. Independent and complementary methods for large-scale structural analysis of mammalian chromatin. Genome Research 17:928-939.
Lee, S. A., D. Ndisang, C. Patel, J. H. Dennis, D. J. Faulkes, C. D'Arrigo, L. Samady, S. Farooqui-Kabir, R. J. Heads, D. S. Latchman, and V. S. Budhram-Mahadeo. 2005. Expression of the Brn-3b transcription factor correlates with expression of HSP-27 in breast cancer biopsies and is required for maximal activation of the HSP-27 promoter. Cancer Research 65:3072-3080.
ENCODE Project Consortium. 2004. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306:636-640.
Samady, L., J. H. Dennis, V. Budhram-Mahadeo, and D. S. Latchman. 2004. Activation of CDK4 gene expression in human breast cancer Cells by the Brn-3b POU family transcription factor. Cancer Biology and Therapy 3:317-323.
Dennis, J. H., V. Budhram-Mahadeo, and D. S. Latchman. 2002. Functional interaction between Brn-3a and Src-1 coactivates Brn-3a-mediated transactivation. Biochemical and Biophysical Research Communications 29:487-495.
Dennis, J. H., V. B. Mahadeo, and D. S. Latchman. 2001. The Brn-3b POU family transcription factor regulates the cellular growth, proliferation and anchorage dependence of MCF7 human breast cancer cells. Oncogene 20:4961-4971.