In multicellular organisms, the unique transcriptional program executed by each cell determines cellular identity. Indeed aberrant gene expression is a causal factor in many common human diseases, including cancer. While the availability of appropriate transcriptional activators or repressors determines whether a gene is transcribed, alteration of chromatin structure plays an important role in maintaining gene expression states. Chromatin is a nucleoprotein structure, consisting of DNA, histones, and non-histone proteins, which packages DNA in the eukaryotic nucleus. Our research uses a combination of molecular biology and bioinformatics to study the roles played by histones, histone chaperones, histone variants, and histone post-translational modifications in preserving active gene expression patterns.
Martin, B.E.J., A.T. Chruscicki, and L.J. Howe. (2018). Transcription promotes the interaction of the FAcilitates Chromatin Transactions (FACT) complex with nucleosomes in S. cerevisiae. Genetics, 210:869-881.
Irwin, N.A.T., B.E.J. Martin, M.J.G. Browne, B. Young, C.J.R., Loewen, A. Flaus, P.J. Keeling, and L.J. Howe. (2018). Viral challenge as a potential driver of histone loss in dinoflagellates. Nature Communications, 9:1535.
Lawrence, M.B., N.C. Coutin, J.K. Choi, J.K., B.E.J. Martin, N.A.T. Irwin, B. Young, B., C.J.R. Loewen, and L.J. Howe. (2017). Histone acetylation, not stoichiometry, regulates linker histone binding in S. cerevisiae. Genetics, 207, 347–355.
Martin, B.E.J., K.L. McBurney, V.E. Maltby, K.N. Jensen, J. Brind’Amour and L.J. Howe. (2017). Histone H3K4 and H3K36 Methylation Independently Recruit the NuA3 Histone Acetyltransferase in Saccharomyces cerevisiae. Genetics, 205, 1113–1123.
McBurney, K.L., A. Leung, J.K. Choi, B.E.J. Martin, N.A.T. Irwin, T. Bartke, C.J. Nelson, and L.J. Howe. (2016). Divergent Residues Within Histone H3 Dictate a Unique Chromatin Structure in Saccharomyces cerevisiae. Genetics. 202:341-9.
Chao, J.T., A.K. Wong, S. Tavassoli, B.P. Young, A.T. Chruscicki, N.N. Fang, L.J. Howe, T. Mayor, L.J. Foster, and C.J. Loewen. (2014). Polarization of the endoplasmic reticulum by ER-septin tethering. Cell, 158: 620-32.
Maltby, V.E., B.J.E. Martin, J.M. Schulze, I. Johnson, T. Hentrich, M.S. Kobor, and L.J. Howe. (2012) Histone H3 Acetylation Negatively Regulates Demethylation of Histone H3K4 by the JmjC Domain Protein, Jhd2. Proc. Nat. Acad. Sci., 109:18505-10.
Maltby, V.E., B.J.E. Martin, J.M. Schulze, I. Johnson, T. Hentrich, A. Sharma, M.S. Kobor, and L.J. Howe. (2012) Histone H3 Lysine 36 Methylation Targets the Isw1b Remodeling Complex to Chromatin. Mol. Cell. Biol., 32:17.
Chruscicki, A.T., V.E. Macdonald, B.P. Young, C.J. Loewen, and L.J. Howe. (2010) Critical Determinants for Chromatin Binding by Saccharomyces cerevisiae Yng1 Exist Outside of the PHD Finger. Genetics, 185:469-77.
Choi, J.K., and L.J. Howe. (2009) Histone acetylation – truth of consequences? Biochemistry and Cell Biology. 87:139-150.
MacDonald, V.E. and L.J. Howe. (2009) Histone acetylation: where to go and how to get there. Epigenetics. 4:139-143.
Choi, J.K., D.E. Grimes, K. Rowe, and L.J. Howe. (2008) Acetylation of Rsc4p by Gcn5p is essential in the absence of histone H3 acetylation. Mol. Cell. Biol. 28: 6967-6972.
Shi, X., I. Kachirskaia, K.L. Walter, J.H. Kuo, A. Lake, F. Davrazou, S.M. Chan, D.E.G. Martin, I.M. Fingerman, S.D. Briggs, L.J. Howe, P.J. Utz, T.G. Kutateladze, A.A. Lugovskoy, M.T. Bedford, and O. Gozani. (2007) Proteome-wide analysis in Saccharomyces cerevisiae identifies several PHD fingers as novel direct and selective binding modules of histone H3 methylated at either lysine 4 or lysine 36. J. Biol. Chem. 282 :2450-5.
Martin, D.E.G., K. Baetz, X. Shi, K.L. Walter, V.E. MacDonald, M.J. Wlodarski, O. Gozani, P. Hieter, and L.J. Howe. (2006) The Yng1p plant homeodomain finger is a methyl-histone binding module that recognizes lysine 4-methylated histone H3. Mol. Cell. Biol. 26 :7871-9.
Martin, D.E.G., D.E. Grimes, K. Baetz, and L.J. Howe. (2006) Methylation of Histone H3 Mediates the Association of the NuA3 Histone Acetyltransferase with Chromatin. Mol. Cell. Biol. 26: 3018-3028.