한빛사논문
- 조회3,449
Abstract
Jung-Ae Kima, Jer-Yuan Hsub,1, M. Mitchell Smithb, and C. David Allisa,2
aLaboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065; and
bDepartment of Microbiology, University of Virginia Health System, Charlottesville, VA 22908
Abstract
A large body of literature provides compelling evidence for the role of evolutionarily conserved core histone residues in various biological processes. However, site-directed mutagenesis of individual residues that are known to be sites of posttranslational modifications often does not result in clear phenotypic defects. In some cases, the combination of multiple mutations can give rise to stronger phenotypes, implying functional redundancy between distinct residues on histones. Here, we examined the “histone redundancy hypothesis” by characterizing double deletion of all pairwise combinations of amino-terminal tails (N-tails) from the four core histones encoded in budding yeast. First, we found that multiple lysine residues on the N-tails of both H2A and H4 are redundantly involved in cell viability. Second, simultaneous deletion of N-tails from H2A and H3 leads to a severe growth defect, which is correlated with perturbed gross chromatin structure in the mutant cells. Finally, by combining point mutations on H3 with deletion of the H2A N-tail, we revealed a redundant role for lysine 4 on H3 and the H2A N-tail in hydroxyurea-mediated response. Altogether, these data suggest that the N-tails of core histones share previously unrecognized, potentially redundant functions that, in some cases are different from those of the widely accepted H2A/H2B and H3/H4 dimer pairs.
acetylation, methylation
Footnotes
1Present Address: NGM Biopharmaceuticals, South San Francisco, CA 94080.
2To whom correspondence should be addressed.
Author contributions: J.-A.K., J.-Y.H., M.M.S., and C.D.A. designed research; J.-A.K. and J.-Y.H. performed research; and J.-A.K. and C.D.A. wrote the paper.
논문정보
- Research article
- 2012년 03월 (BRIC 등록일 )
- 국외 연구진
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