Abstract
The connections between various nuclear processes and specific histone posttranslational modifications are dependent to a large extent on the acquisition of those modifications after histone synthesis. The reestablishment of histone posttranslational modifications after S phase is especially critical for H3K9 and H3K27 trimethylation, both of which are linked with epigenetic memory and must be stably transmitted from one cellular generation to the next. This report uses a proteomic strategy to interrogate how and when the cell coordinates the formation of histone posttranslational modifications during division. Paramount among the findings is that H3K9 and H3K27 trimethylation begins during S phase but is completed only during the subsequent G1 phase via two distinct pathways from the unmodified and preexisting dimethylated states. In short, we have systematically characterized the temporal origins and methylation pathways for histone posttranslational modifications during the cell cycle.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.06673-11.
ACKNOWLEDGMENTS
We thank Paul Schedl for incisive and invaluable discussions; Eric Chan and Gary LeRoy for the design of the custom gene expression microarray; Mario Andres Blanco, Peter DiMaggio, and Donna Storton for microarray analysis assistance; Wenyun Lu and Joshua Rabinowitz for SRM analysis; Christina DeCoste and Christi O'Donnell for flow cytometry; Shu Lin, Shelby Blythe, and Olivier Devergne for qRT-PCR assistance; and Girish Deshpande, Michelle Gonzales-Cope, Shu Lin, Wei Li, Elizabeth Gavis, Yali Dou, Robert Schneider, and Or Gozani for reading the manuscript.
Barry M. Zee is supported by the National Science Foundation (NSF) Graduate Research Fellowship Program and Sigma Xi grants-in-aid research. Laura-Mae P. Britton is funded by the Department of Molecular Biology at Princeton University. Daniel Wolle is funded by an NIH training grant. Devorah M. Haberman is funded by the Department of Chemistry at Princeton University. Benjamin A. Garcia gratefully acknowledges support from an NSF Early Faculty Career award, NSF grant CBET-0941143, and an NIH Director's New Innovator award (DP2OD007447) from the Office of the Director, NIH.