Dataset Information

Mutagenesis of pairwise combinations of histone amino-terminal tails reveals functional redundancy in budding yeast.

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.

SUBMITTER: Kim JA

PROVIDER: S-EPMC3326485 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Mutagenesis of pairwise combinations of histone amino-terminal tails reveals functional redundancy in budding yeast.

Kim Jung-Ae JA Hsu Jer-Yuan JY Smith M Mitchell MM Allis C David CD

Proceedings of the National Academy of Sciences of the United States of America 20120326 15

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 examine ...[more]

PMID: 22451923

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Project description:The frequent dispensability of duplicated genes in budding yeast is heralded as a hallmark of genetic robustness contributed by genetic redundancy. However, theoretical predictions suggest such backup by redundancy is evolutionarily unstable, and the extent of genetic robustness contributed from redundancy remains controversial. It is anticipated that, to achieve mutual buffering, the duplicated paralogs must at least share some functional overlap. However, counter-intuitively, several recent studies reported little functional redundancy between these buffering duplicates. The large yeast genetic interactions released recently allowed us to address these issues on a genome-wide scale. We herein characterized the synthetic genetic interactions for ?500 pairs of yeast duplicated genes originated from either whole-genome duplication (WGD) or small-scale duplication (SSD) events. We established that functional redundancy between duplicates is a pre-requisite and thus is highly predictive of their backup capacity. This observation was particularly pronounced with the use of a newly introduced metric in scoring functional overlap between paralogs on the basis of gene ontology annotations. Even though mutual buffering was observed to be prevalent among duplicated genes, we showed that the observed backup capacity is largely an evolutionarily transient state. The loss of backup capacity generally follows a neutral mode, with the buffering strength decreasing in proportion to divergence time, and the vast majority of the paralogs have already lost their backup capacity. These observations validated previous theoretic predictions about instability of genetic redundancy. However, departing from the general neutral mode, intriguingly, our analysis revealed the presence of natural selection in stabilizing functional overlap between SSD pairs. These selected pairs, both WGD and SSD, tend to have decelerated functional evolution, have higher propensities of co-clustering into the same protein complexes, and share common interacting partners. Our study revealed the general principles for the long-term retention of genetic redundancy.

Dataset Information

Mutagenesis of pairwise combinations of histone amino-terminal tails reveals functional redundancy in budding yeast.

Publications

Mutagenesis of pairwise combinations of histone amino-terminal tails reveals functional redundancy in budding yeast.

Similar Datasets

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