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.

Using the innate immune response of macrophages to bacterial, viral, and fungal infection as a model, I have established a system in which I can monitor the consequence to chromatin structure of infection, as well as the temporal regulation of this response (immediate, early and late responses). I use this system to investigate the response of approximately 100 genes central to inflammation. My goals are to understand (1) local chromatin structural changes, (2) the chromatin modifying complexes responsible for these changes, and (3) the larger scale organizational changes that alter the distribution and accessibility of chromatin in the nucleus.

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.

Graduate Students:

Druliner, Brooke
Sexton, Brittany
Spetman, Brian
Vera, Daniel

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