Functional genomics

Genome-wide prediction of conserved and nonconserved enhancers by histone acetylation patterns. Roh, T.-Y. et al. Genome Res. 29 November 2006 (doi: 10.1101/gr.5767907)

This study combines epigenomics and comparative genomics to improve the identification of functional non-coding sequences. The authors identified thousands of sequences that are conserved between humans and pufferfish, or between humans and mice, and that also correspond to islands of histone H3 diacetylation in human T cells. Many of the conserved sequences were found to have enhancer activity in T cells, and patterns of epigenetic modification were conserved in the mouse. This combined approach therefore aids the search for functional elements from among large numbers of conserved sequences.

Molecular evolution

Robustness–epistasis link shapes the fitness landscape of a randomly drifting protein. Bershtein, S. et al. Nature 19 November 2006 (doi: 10.1038/nature05385)

Bershtein and colleagues subjected a bacterial enzyme to random mutational drift and purifying selection. The resulting effects on fitness indicated negative epistasis, in which the combined effect of mutations is greater than expected from their individual impacts on fitness. This negative epistasis was correlated with mutational robustness. The authors propose a model of robustness in which mutational effects are buffered up to a certain threshold, above which stability breaks down and the deleterious effects are unleashed to their full extent.

RNA world

A late-acting quality control process for mature eukaryotic rRNAs. LaRiviere, F. J. et al. Mol. Cell 24, 619–626 (2006)

The existence of quality-control pathways for mRNAs is well established; this study now shows that ribosomal RNAs (rRNAs) are also subject to such monitoring mechanisms. The authors showed that rRNAs that contain point mutations in sites that are essential for ribosome function are significantly downregulated in Saccharomyces cerevisiae. The mechanism that is involved results in decreased stability of rRNAs that have already been assembled into ribosomes or ribosomal subunits. This provides a means by which eukaryotic cells might ensure the structural and functional integrity of the protein-translating machinery.

Sex chromosomes

Clustered DNA motifs mark X chromosomes for repression by a dosage compensation complex. McDonel, P. et al. Nature 444, 614–618 (2006)

In Caenorhabditis elegans hermaphrodites, expression from each X chromosome is repressed by half so that total expression is the same as that in males, which possess only one X chromosome. These authors have identified the sequence elements that mark the X chromosomes for such repression by the dosage compensation complex. These rex (recruitment element on X) sites contain at least two motifs, which are not enriched on the X chromosome, but the distribution of which within rex sites marks the correct chromosomes for repression.