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Science 16 February 1990:
Vol. 247. no. 4944, pp. 841 - 845
DOI: 10.1126/science.2106160

Articles

Science, Vol 247, Issue 4944, 841-845
Copyright © 1990 by American Association for the Advancement of Science


articles

Genetic analysis of histone H4: essential role of lysines subject to reversible acetylation

PC Megee, BA Morgan, BA Mittman, and MM Smith

Department of Microbiology, School of Medicine, University of Virginia, Charlottesville 22908.

The nucleosome is the fundamental unit of assembly of the chromosome and reversible modifications of the histones have been suggested to be important in many aspects of nucleosome function. The structure-function relations of the amino-terminal domain of yeast histone H4 were examined by the creation of directed point mutations. The four lysines subject to reversible acetylation were essential for histone function as the substitution of arginine or asparagine at these four positions was lethal. No single lysine residue was completely essential since arginine substitutions at each position were viable, although several of these mutants were slower in completing DNA replication. The simultaneous substitution of glutamine for the four lysine residues was viable but conferred several phenotypes including mating sterility, slow progression through the G2/M period of the division cycle, and temperature-sensitive growth, as well as a prolonged period of DNA replication. These results provide genetic proof for the roles of the H4 amino-terminal domain lysines in gene expression, replication, and nuclear division.


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Histone H4 and the maintenance of genome integrity..
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Silencers and domains of generalized repression.
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Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila..
J R Bone, J Lavender, R Richman, M J Palmer, B M Turner, and M I Kuroda (1994)
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Origin recognition complex (ORC) in transcriptional silencing and DNA replication in S. cerevisiae.
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Transcriptional silencing in yeast is associated with reduced nucleosome acetylation..
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A RAP1-interacting protein involved in transcriptional silencing and telomere length regulation..
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An origin of DNA replication and a transcription silencer require a common element.
D. Rivier and J Rine (1992)
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Stable nucleosome positioning and complete repression by the yeast alpha 2 repressor are disrupted by amino-terminal mutations in histone H4..
S Y Roth, M Shimizu, L Johnson, M Grunstein, and R T Simpson (1992)
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Proteolytic removal of core histone amino termini and dephosphorylation of histone H1 correlate with the formation of condensed chromatin and transcriptional silencing during Tetrahymena macronuclear development..
R Lin, R G Cook, and C D Allis (1991)
Genes & Dev. 5, 1601-1610
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Cloning and Characterization of a Novel Human Class I Histone Deacetylase That Functions as a Transcription Repressor.
E. Hu, Z. Chen, T. Fredrickson, Y. Zhu, R. Kirkpatrick, G.-F. Zhang, K. Johanson, C.-M. Sung, R. Liu, and J. Winkler (2000)
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