Catherine A. Musselman, PhD

Portrait
Assistant Professor of Biochemistry

Contact Information

Primary Office: 4-452 BSB
Iowa City, IA 52242
319-353-5888

Education

BS, Chemistry, University of Colorado at Denver
MS, Chemistry, University of Michigan
PhD, Chemistry, University of Michigan

Fellow, Chemistry, University of Colorado, Denver School of Medicine

Education/Training Program Affiliations

Department of Biochemistry PhD

Research Summary

The genome of every eukaryotic cell resides in complex with histone proteins to form chromatin. Though originally thought to just package the genome into the nucleus, chromatin structure is now recognized to play an active role in the regulation of all DNA templated processes in eukaryotes. Such regulation requires the spatial and temporal alteration of chromatin structure, which is mediated by the chemical modification of histones and DNA as well as by the action of a large number of chromatin associated cofactors. My lab is interested in deciphering mechanisms of chromatin structure modulation and how misregulation of these pathways is associated with disease. Specifically, our goal is to elucidate, on the molecular level, the details of how cofactors target nucleosomes, especially in response to histone modification, and how this leads to the regulation of genes. Such knowledge will enhance our fundamental understanding of chromatin biology as well as reveal the etiology of many human diseases with the aim of eventually aiding in the development of targeted therapeutics. We employ NMR spectroscopy, X-ray crystallography as well as a variety of other biophysical and biochemical techniques to approach these questions.

Publications

Morrison, E., Sanchez, J., Ronana, J., Farrell, D., Varzavand, K., Johnson, J., Gu, B., Crabtree, G. & Musselman, C. (2017). DNA binding drives the association of BRG1/hBRM bromadomains with nucleosomes. Nature Communications, 8(16080).

Xing, S., Li, F., Zeng, Z., Zhao, Y., Yu, S., Shan, Q., Li, Y., Phillips, F. C., Maina, P. K., Qi, H. H., Liu, C., Zhu, J., Pope, R. M., Musselman, C. A., Zeng, C., Peng, W. & Xue, H. H. (2016). Tcf1 and Lef1 transcription factors establish CD8(+) T cell identity through intrinsic HDAC activity. Nature immunology, 17(6), 695-703. PMID: 27111144.

Musselman, C. A., Kutateladze, T. G. (2016). Preparation, Biochemical Analysis, and Structure Determination of Methyllysine Readers. Methods in enzymology, 573, 345-62. PMID: 27372761.

Morrison, E., Musselman, C. (2016). The role of PHD fingers in chromatin signaling: Mechanisms and functional consequences of the recognition of histone and non-histone targets. Elsevier, 127-147.

Tong, Q., Cui, G., Botuyan, M. V., Rothbart, S. B., Hayashi, R., Musselman, C. A., Singh, N., Appella, E., Strahl, B. D., Mer, G. & Kutateladze, T. G. (2015). Structural plasticity of methyllysine recognition by the tandem tudor domain of 53BP1. Structure (London, England : 1993), 23(2), 312-21. PMID: 25579814.

Doyle, K. (2015). Unpacking the epigenetics of cancer. Genetic Engineering & Biotechnology News.

Musselman, C., Khorasanizadeh, S. & Kutateladze, T. (2014). Towards understanding methyllysine readout. Biochim Biophys Acta, 1839(8), 686-93. PMID: 24727128.

Wang, C., Chen, Z., Hong, X., Ning, F., Liu, H., Zang, J., Yan, X., Kemp, J., Musselman, C., Kutateladze, T., Zhao, R., Jiang, C. & Zhang, G. (2014). The structural basis of urea-induced protein unfolding in ß-catenin. Acta Crystallogr D Biol Crystallogr, 70(11), 2840-7. PMID: 25372676.

Allen, H., Daze, K., Shimbo, T., Lai, A., Musselman, C., Sims, J., Wade, P., Hof, F. & Kutateladze, T. (2014). Inhibition of histone binding by supramolecular hosts. Biochem J, 459(3), 505-12. PMID: 24576085.

Ezhov, R., Metzel, G., Mukhina, O., Musselman, C., Kutateladze, T., Gustafson, T. & Kutateladze, A. (2014). Photoactive Spatial Proximity Probes for Binding Pairs with Epigenetic Marks. J Photochem Photobiol A Chem, 290, 101-108. PMID: 25197204.

Musselman, C. A., Gibson, M. D., Hartwick, E. W., North, J. A., Gatchalian, J., Poirier, M. G. & Kutateladze, T. G. (2013). Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility. Nat Commun,(4), 2969. PMID: 24352064.

Oliver, S. S., Musselman, C. A., Srinivasan, R., Svaren, J. P., Kutateladze, T. G. & Denu, J. M. (2012). Multivalent recognition of histone tails by the PHD fingers of CHD5. Biochemistry, 51(33), 6534-44. PMID: 22834704.

Musselman, C. A., Ramirez, J., Sims, J. K., Mansfield, R. E., Oliver, S. S., Denu, J. M., Mackay, J. P., Wade, P. A., Hagman, J. & Kutateladze, T. G. (2012). Bivalent recognition of nucleosomes by the tandem PHD fingers of the CHD4 ATPase is required for CHD4-mediated repression. Proceedings of the National Academy of Sciences, 109(3), 787-792. PMID: 22215588.

Musselman, C. A., Avvakumov, N., Watanabe, R., Abraham, C. G., Lalonde, M., Hong, Z., Allen, C., Roy, S., Nuñez, J. K., Nickoloff, J., Kulesza, C. A., Yasui, A., Côté, J. & Kutateladze, T. G. (2012). Molecular basis for H3K36me3 recognition by the Tudor domain of. Natural Structure Molecular Biology, 19, 1266-1272.

Musselman, C. A., Lalonde, M. E., Cote, J. & Kutateladze, T. G. (2012). Perceiving the epigenetic landscape through histone readers. Nature structural & molecular biology, 19(12), 1218-27. PMID: 23211769.

Musselman, C. A., Ramirez, J., Sims, J. K., Mansfield, R. E., Oliver, S. S., Denu, J. M., Mackay, J. P., Wade, P. A., Hagman, J. & Kutateladze, T. G. (2012). Bivalent Recognition of a Single Nucleosome by the Tandem PHD Fingers of CHD4 is Required for CHD4-Mediated Repression. (Vols. 102). (3), pp. 480a. Biophysical Journal.

Hagman, J., Ramirez, J., Dege, C., Eshelman, E., Musselman, C. A. & Kutateladze, T. G. (2012). Mi-2/NuRD chromatin remodeling complexes maintain transcriptional attenuation during B cell development. (Vols. 188). Journal of Immunology.

Scott, J. L., Musselman, C. A., Adu-Gyamfi, E., Kutateladze, T. G. & Stahelin, R. V. (2012). Emerging methodologies to investigate lipid-protein interactions. Integrative biology : quantitative biosciences from nano to macro, 4(3), 247-58. PMID: 22327461.

Jones, R., Abed, J. (2012). H3K36me3 key to Polycomb-mediated gene slicing in lineage specification. Natural Struct. Mol. Biol., 19(12), 1214.

Mansfield, R. E., Musselman, C. A., Kwan, A. H., Oliver, S. S., Garske, A. L., Davrazou, F., Denu, J. M., Kutateladze, T. G. & Mackay, J. P. (2011). Plant homeodomain (PHD) fingers of CHD4 are histone H3-binding modules with preference for unmodified H3K4 and methylated H3K9. The Journal of biological chemistry, 286(13), 11779-91. PMID: 21278251.

Musselman, C. A., Kwan, A., Mansfield, R., Mackay, J. & Kutateladze, T. G. (2011). The Tandem PHD Fingers of Chd4 Bind Synergistically to Histone H3. Biophysical Journal, 100(3), 67a.

Musselman, C. A., Kutateladze, T. G. (2011). Methyl fingerprinting of the nucleosome reveals the molecular mechanism of high-mobility group nucleosomal-2 (HMGN2) association. (Vols. 108). (30), pp. 12189-12190. Proceedings of the National Academy of Sciences. PMID: 21753078.

Mansfield, R., Musselman, C., Davrazou, F., Garske, A., Kwan, A., Denu, J., Kutateladze, T. & Mackay, J. (2011). The PHD fingers of CHD4 are histone H3-binding modules with preference for unmodified H3K4 and methylated H3K9. Journal of Biological Chemistry, 286(13), 11779-91.

Musselman, C. A., Kutateladze, T. G. (2011). Handpicking epigenetic marks with PHD fingers. Nucleic acids research, 39(21), 9061-71. PMID: 21813457.

Chang, P., Hom, R. A., Musselman, C. A., Zhu, L., Kuo, A., Gozani, O., Kutateladze, T. G. & Cleary, M. L. (2010). Binding of the MLL PHD3 finger to histone H3K4me3 is required for MLL-dependent gene transcription. Journal of Molecular Biology, 400(2), 137-144. PMID: 20452361.

Musselman, C. A. (2010). Pathways for Double-strand Break Repair in Genetically Unstable Z-DNA-forming Sequences.

Hom, R. A., Chang, P., Roy, S., Musselman, C. A., Glass, K. C., Selezneva, A. I., Gozani, O., Ismagilov, R. F., Cleary, M. L. & Kutateladze, T. G. (2010). Molecular mechanism of MLL PHD3 and RNA recognition by the Cyp33 RRM domain. Journal of Molecular Biology, 400(2), 145-154.

Musselman, C., Zhang, Q., Al-Hashimi, H. & Andricioaei, I. (2010). Referencing strategy for the direct comparison of nuclear magnetic resonance and molecular dynamics motional parameters in RNA. The journal of physical chemistry. B, 114(2), 929-39. PMID: 20039757.

Garske, A. L., Oliver, S. S., Wagner, E. K., Musselman, C. A., LeRoy, G., Garcia, B. A., Kutateladze, T. G. & Denu, J. M. (2010). Combinatorial profiling of chromatin binding modules reveals multisite discrimination. Nature chemical biology, 6(4), 283-90. PMID: 20190764.

Chang, P., Hom, R., Musselman, C., Zhu, L., Kuo, A., Gozani, O., Kutateladze, T. & Cleary, M. (2010). Binding of the MLL PHD3 finger to histone H3K4me3 is required for MLL dependent gene transcription. Journal of Molecular Biology, 400(2), 137-144.

Musselman, C. A., Mansfield, R. E., Garske, A. L., Davrazou, F., Kwan, A. H., Oliver, S. S., O'Leary, H., Denu, J. M., Mackay, J. P. & Kutateladze, T. G. (2010). Binding of the CHD4 PHD2 Finger to Histone H3 is Modulated by Covalent Modifications. Biophysical Journal, 98(3(1)), 475A. PMID: 19624289.

Roy, S., Musselman, C. A., Kachirskaia, I., Hayashi, R., Glass, K. C., Nix, J. C., Gozani, O., Appella, E. & Kutateladze, T. G. (2010). Structural insight into p53 recognition by the 53BP1 tandem Tudor domain. Journal of Molecular Biology, 398(4), 489-496. PMID: 20307547.

Garske, A. L., Oliver, S. S., Wagner, E. K., Musselman, C. A., LeRoy, G., Garcia, B. A., Kutateladze, T. G. & Denu, J. M. (2010). Combinatorial profiling of chromatin binding modules reveals multisite discrimination. Nature Chemical Biology, 6(4), 283-290. PMID: 20190764.

Musselman, C. A., Kutateladze, T. G. (2009). PHD fingers: epigenetic effectors and potential drug targets. Molecular Interventions, 9(6), 314-323.

Musselman, C. A., Mansfield, R. E., Garsket, A. L., Davrazou, F., Kwan, A. H., Oliver, S. S., O'Leary, H., Denu, J. M., Mackay, J. P. & Kutateladze, T. G. (2009). Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications. Biochem J, 423(2), 179-187.

Kutateladze, T. G., Champagne, K. S., Pena, P. V., Musselman, C. A., Hung, T., Saksouk, N., Cote, J. & Gozani, O. (2009). The structural insight into the biological role of PHD fingers. Federation Amer Soc Exp Biol, 23.

Peña, P. V., Musselman, C. A., Kuo, A. J., Gozani, O. & Kutateladze, T. G. (2009). NMR assignments and histone specificity of the ING2 PHD finger. Magnetic Resonance in Chemistry, 47(4), 352-358. PMID: 19184981.

He, J., Vora, M., Haney, R. M., Filonov, G. S., Musselman, C. A., Burd, C. G., Kutateladze, A. G., Verkhusha, V. V., Stahelin, R. V. & Kutateladze, T. G. (2009). Membrane insertion of the FYVE domain is modulated by pH. Proteins: Structure, Function, and Bioinformatics, 76(4), 852-860. PMID: 19296456.

Dethoff, E. A., Hansen, A. L., Musselman, C. A., Watt, E. D., Andricioaei, I. & Al-Hashimi, H. M. (2008). Characterizing complex dynamics in the transactivation response element apical loop and motional correlations with the bulge by NMR, molecular dynamics, and mutagenesis. Biophysical Journal, 95(8), 3906-3915. PMID: 18621815.

Musselman, C. A., Al-Hashimi, H. M. & Andricioaei, I. (2007). iRED analysis of TAR RNA reveals motional coupling, long-range correlations, and a dynamical hinge. Biophysical Journal, 93(2), 411-422. PMID: 17449677.

Bailor, M. H., Musselman, C. A., Hansen, A. L., Gulati, K., Patel, D. J. & Al-Hashimi, H. M. (2007). Characterizing the relative orientation and dynamics of RNA A-form helices using NMR residual dipolar couplings. Nature Protocols, 2(6), 1536-1546. PMID: 17571061.

Musselman, C. A., Pitt, S. W., Gulati, K., Foster, L. L., Andricioaei, I. & Al-Hashimi, H. M. (2006). Impact of static and dynamic A-form heterogeneity on the determination of RNA global structural dynamics using NMR residual dipolar couplings. Journal of Biomolecular NMR, 36(4), 235-249. PMID: 17077936.