@article{7a3a8f10ed4e4e83977ca61be27839bd,
title = "Recognition of a mononucleosomal histone modification pattern by BPTF via multivalent interactions",
abstract = "Little is known about how combinations of histone marks are interpreted at the level of nucleosomes. The second PHD finger of human BPTF is known to specifically recognize histone H3 when methylated on lysine 4 (H3K4me2/3). Here, we examine how additional heterotypic modifications influence BPTF binding. Using peptide surrogates, three acetyllysine ligands are indentified for a PHD-adjacent bromodomain in BPTF via systematic screening and biophysical characterization. Although the bromodomain displays limited discrimination among the three possible acetyllysines at the peptide level, marked selectivity is observed for only one of these sites, H4K16ac, in combination with H3K4me3 at the mononucleosome level. In support, these two histone marks constitute a unique trans-histone modification pattern that unambiguously resides within a single nucleosomal unit in human cells, and this module colocalizes with these marks in the genome. Together, our data call attention to nucleosomal patterning of covalent marks in dictating critical chromatin associations.",
author = "Ruthenburg, {Alexander J.} and Haitao Li and Milne, {Thomas A.} and Scott Dewell and McGinty, {Robert K.} and Melanie Yuen and Beatrix Ueberheide and Yali Dou and Muir, {Tom W.} and Patel, {Dinshaw J.} and Allis, {C. David}",
note = "Funding Information: We would like to thank the staff at beamline 24ID-C of the Advanced Photon Source at the Argonne National Laboratory and the staff at beamline X29 of the National Synchrotron Light Source at Brookhaven National Laboratory, supported by the US Department of Energy, for assistance with data collection. This work is based upon research conducted at the Northeastern Collaborative Access Team (NE-CAT) beamlines of the Advanced Photon Source and the Macromolecular Crystallography Research Resource (PXRR) at the National Synchrotron Light Source, which are supported by the National Center for Research Resources at the National Institutes of Health. We would like to thank L. Liang for assistance in protein production and crystallization of BPTF H4 peptide complexes; H.A. Zebrowski for assistance in the preparation of the SPOT membrane; S.S. Yi of the Microchemistry and Proteomics Core at Memorial-Sloan Kettering Cancer Center for synthesis of peptides; Y. Wei of the Rockefeller Chemical Biology Spectroscopy center for use of their Biacore instrument; S. Yokoyama and H. Kurumizaka for an expression construct bearing codon optimized histone H4; K. Chiang for his 3_601_3_x32 repeat plasmid; M.Vila-Perello for HF cleavage of Boc-peptides; H. Dormann for HP1-chromodomain recombinantly produced protein; H. Yu of the Rockefeller Proteomics Core for MS assistance; C. Wu for the human BPTF cDNA; and L. Baker, F. Casadio, J. Denu, P.W. Lewis, K-M. Noh, R.G. Roeder, R. Sadeh, D. Shechter, T. Swigut, G.G. Wang, and J. Wysocka for valuable discussions and scientific input. A.J.R. is supported by Irvington Institute Fellowship Program of the Cancer Research Institute, and R.K.M. is supported by an MSTP grant. This work was supported by a MERIT grant from the NIH and funds from The Rockefeller University to C.D.A., as well as funds from the Leukemia and Lymphoma Society and Starr Foundation to C.D.A. and D.J.P. D.J.P. is supported by funds from the Abby Rockefeller Mauze Trust and the Dewitt Wallace and Maloris Foundations, and T.W.M. is supported by an award from the NIH. D.J.P. is a consultant in GlaxoSmithKline's epigenetic programs. ",
year = "2011",
month = may,
day = "27",
doi = "10.1016/j.cell.2011.03.053",
language = "English (US)",
volume = "145",
pages = "692--706",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}