The chromatin state of a gene encodes the regulatory information that controls its expression. This information exists in the locations and structures of the nucleosomes as well as in the many covalent modifications present on the packaging proteins, the histones. A given chromatin state is created, maintained and altered by the combined action of chromatin remodeling enzymes, histone modifying enzymes and histone binding proteins. An ability to rapidly transition between different chromatin states is necessary to ensure rapid transcriptional responses to developmental and environmental signals and an ability to stably maintain chromatin states is necessary to lock in the transcriptional patterns of differentiated cells.

We are interested in understanding how the information content of chromatin states is regulated by the different factors that catalyze rapid changes in chromatin structure as well the factors that help maintain defined chromatin structures. We use a combination of biophysical and structural approaches to address these questions.

Leonard JD, and Narlikar GJ. (2015) A Nucleotide-Driven Switch Regulates Flanking DNA Length Sensing by a Dimeric Chromatin Remodeler Molecular Cell Accepted. Canzio D, Larson A, Narlikar GJ. (2014) Mechanisms of functional promiscuity by HP1 proteins. Trends Cell Bio. 24(6):377-386. Racki LR, Naber N, Pate E, Leonard J, Cooke R, Narlikar GJ. (2014) The histone H4 tail regulates the conformation of the ATP-binding pocket in the SNF2h chromatin remodeling enzyme. J. Mol. Bio. 426:2034-44. Narlikar G.J., Sundaramoorthy R., Owen-Hughes T. (2013) Mechanisms and Functions of ATP-Dependent Chromatin-Remodeling Enzymes. Cell 154(3):490-503. Al-Sady B., Madhani H.D., Narlikar G.J. (2013) Division of labor between the chromodomains of HP1 and Suv39 methylase enables coordination of heterochromatin spread. Mol Cell 51(1):80-91. Shiau C., Trnka M.J., Bozicevic A., Ortiz-Torres I., Al-Sady B., Burlingame A.L., Narlikar G.J., Fujimori D.G. (2013) Reconstitution of nucleosome demethylation and catalytic properties of a Jumonji histone demethylase. Chem Biol 20(4):494-9. Canzio D., Liao M., Naber N., Pate E., Larson A., Wu S., Marina D.B., Garcia J.F., Madhani H.D., Cooke R., Schuck P., Cheng Y., Narlikar G.J. (2013) A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly. Nature 496(7445):377-81. Rougemaille M., Braun S., Coyle S., Dumesic P.A., Garcia J.F., Isaac R.S., Libri D., Narlikar G.J., Madhani H.D. (2012) Ers1 links HP1 to RNAi. Proc. Natl. Acad. Sci. USA 109(28):11258-63. Shahian T., Narlikar G.J. (2012) Analysis of changes in nucleosome conformation using fluorescence resonance energy transfer. Methods Mol Biol 833:337-49. Armache K.J., Garlick J.D., Canzio D., Narlikar G.J., Kingston R.E. (2011) Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 Å resolution. Science 334(6058):977-82. Charles, G.M., Chen, C., Shih, S.C., Collins, S.R., Beltrao, P., Zhang, X., Sharma, T., Tan, S., Burlingame, A.L., Krogan, N.J., Madhani, H.D., Narlikar, G.J. (2011) Site-specific acetylation mark on an essential chromatin-remodeling complex promotes resistance to replication stress. Proc. Natl. Acad. Sci. USA 108:10620-5. Canzio, D., Chang, E.Y., Shankar, S., Kuchenbecker, K.M., Simon, M.D., Madhani, H.D., Narlikar G.J., Al-Sady, B. (2011) Chromodomain-Mediated Oligomerization of HP1 Suggests a Nucleosome-Bridging Mechanism for Heterochromatin Assembly. Molecular Cell 41:67-81. Rowe, C.E., Narlikar G.J. (2010) The ATP-Dependent Remodeler RSC Transfers Histone Dimers and Octamers through the Rapid Formation of an Unstable Encounter Intermediate. Biochemistry 49:9882-90. Racki, L.R., Yang, J.G., Nariman, N., Partensky, P.D., Acevedo, A., Purcell, T.J., Cooke, R., Cheng, Y. and Narlikar, G.J. (2009). The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes. Nature 462:1016-1021. Blosser, T.Y., Yang, J.G., Stone, M.D., Narlikar, G.J. and Zhuang, X. (2009). Dynamics of nucleosome remodelling by individual ACF complexes. Nature 462:1022-1027. Partensky, P.D. and Narlikar, G.J. (2009). Chromatin Remodelers Act Globally, Sequence Positions Nucleosomes Locally. J Mol Bio 391:12-25. Chang, E.Y., Ferreira, H., Somers, J., Nusinow, D.A., Owen-Hughes, T. and Narlikar, G.J. (2008). MacroH2A allows ATP-dependent chromatin remodeling by SWI/SNF and ACF complexes but specifically reduces recruitment of SWI/SNF. Biochemistry 47:13726–13732. Racki, L.R. and Narlikar, G.J. (2008). ATP-dependent chromatin remodeling enzymes: two heads are not better, just different. Curr Opin Genet Dev 18:137-144. Simon, M.D., Chu, F., Racki, L.R., de la Cruz, C.C., Burlingame, A.L., Panning, B., Narlikar, G.J., Shokat, K.M. (2007). The site-specific installation of methyl-lysine analogs into recombinant histones. Cell 128:1003-1012. Yang, J.G. and Narlikar, G.J. (2007). FRET-based methods to study ATP-dependent changes in chromatin structure. Methods 41:291-295. Yang, J., Madrid T.S., Sevastopoulos, E. and Narlikar, G.J. (2006). The chromatin-remodeling enzyme ACF is an ATP-dependent DNA length sensor that regulates nucleosome spacing. Nature SMB 13:1078-1083. He, X., Fan, H.Y., Narlikar, G.J. and Kingston, R.E. (2006). Human ACF1 alters the remodeling strategy of SNF2h. J Biol Chem 281:28636-28647. Mahajan, M.C., Narlikar, G.J., Boyapaty, G., Kingston, R.E. and Weissman, S.M. (2005). Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SWI/SNF form a chromatin remodeling complex at the {beta}-globin locus control region. Proc. Natl. Acad. Sci. USA 102:15012-15017. Fan, H-Y., Narlikar, G.J. and Kingston, R.E (2004). Noncovalent modification of chromatin: different remodeled products with different ATPase domains. Cold Spring Harb Symp Quant Biol 69:183-192. Fan, H-Y., He, X., Kingston, R.E. and Narlikar, G.J. (2003). Distinct Strategies to Make Nucleosomal DNA Accessible. Mol Cell 11:1311-1322.