TY - JOUR
T1 - Chromatin signaling to kinetochores
T2 - Transregulation of Dam1 methylation by histone H2B ubiquitination
AU - Latham, John A.
AU - Chosed, Renée J.
AU - Wang, Shanzhi
AU - Dent, Sharon Y.R.
N1 - Funding Information:
J.A.L. was supported in part by a fellowship by the American Legion Auxiliary. Funding for R.J.C. as an Odyssey Fellow was supported by the Odyssey Program and the Theodore N. Law Endowment for Scientific Achievement at the University of Texas M.D. Anderson Cancer Center. Aspects of this work were supported by NIH grant GM51189 and a grant from the Robert A. Welch Foundation (G1371) to S.Y.R.D. DNA sequencing for this project was done in the UTMDACC DNA Analysis Facility, supported by Cancer Center Support Grant NCI CA16672. We thank the members of the Dent lab, especially Andria Schibler, Rebecca Lewis, Jill Butler, and Marenda Wilson-Pham for their suggestions as well as Fred Winston, Mitch Smith, and Kevin Morano for insightful comments. We are also grateful to Drs. Ambro van Hoof, Mary Ann Osley, Sue Biggins, Brian Strahl, and Peter Nagy for generously providing yeast strains, plasmids, and antibodies.
PY - 2011/9/2
Y1 - 2011/9/2
N2 - Histone H3K4 trimethylation by the Set1/MLL family of proteins provides a hallmark for transcriptional activity from yeast to humans. In S. cerevisiae, H3K4 methylation is mediated by the Set1-containing COMPASS complex and is regulated in trans by prior ubiquitination of histone H2BK123. All of the events that regulate H2BK123ub and H3K4me are thought to occur at gene promoters. Here we report that this pathway is indispensable for methylation of the only other known substrate of Set1, K233 in Dam1, at kinetochores. Deletion of RAD6, BRE1, or Paf1 complex members abolishes Dam1 methylation, as does mutation of H2BK123. Our results demonstrate that Set1-mediated methylation is regulated by a general pathway regardless of substrate that is composed of transcriptional regulatory factors functioning independently of transcription. Moreover, our data identify a node of regulatory crosstalk in trans between a histone modification and modification on a nonhistone protein, demonstrating that changing chromatin states can signal functional changes in other essential cellular proteins and machineries.
AB - Histone H3K4 trimethylation by the Set1/MLL family of proteins provides a hallmark for transcriptional activity from yeast to humans. In S. cerevisiae, H3K4 methylation is mediated by the Set1-containing COMPASS complex and is regulated in trans by prior ubiquitination of histone H2BK123. All of the events that regulate H2BK123ub and H3K4me are thought to occur at gene promoters. Here we report that this pathway is indispensable for methylation of the only other known substrate of Set1, K233 in Dam1, at kinetochores. Deletion of RAD6, BRE1, or Paf1 complex members abolishes Dam1 methylation, as does mutation of H2BK123. Our results demonstrate that Set1-mediated methylation is regulated by a general pathway regardless of substrate that is composed of transcriptional regulatory factors functioning independently of transcription. Moreover, our data identify a node of regulatory crosstalk in trans between a histone modification and modification on a nonhistone protein, demonstrating that changing chromatin states can signal functional changes in other essential cellular proteins and machineries.
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U2 - 10.1016/j.cell.2011.07.025
DO - 10.1016/j.cell.2011.07.025
M3 - Article
C2 - 21884933
AN - SCOPUS:80052288217
SN - 0092-8674
VL - 146
SP - 709
EP - 719
JO - Cell
JF - Cell
IS - 5
ER -