Genomics

Mapping the human methylome

Using different reductionist approaches, two groups now map the human methylome at nucleotide resolution. Using reduced representation bisulphate sequencing, Meissner et al. charted the methylomes of embryonic stem cells and primary neuronal cells, providing key insights into stem cell differentiation. With the aid of a new computational tool called Batman, Down et al. used DNA methylation immunoprecipitation coupled to high-throughput sequencing to chart the methylome of human sperm.

Down, T.A. et al. Nat. Biotechnol. 26, 779–785 (2008).

Meissner, A. et al. Nature 454, 766–770 (2008).

Proteomics

Mice on a SILAC diet

Stable isotope labeling with amino acids in cell culture (SILAC) is a metabolic labeling technique used to quantitatively compare proteomic differences in two cell populations via mass spectrometry. Krüger et al. now extend the SILAC method to a mammalian model organism: the mouse. They found that mice could be SILAC-treated for several generations without any detrimental effects, and the labels were incorporated into all organ proteomes.

Krüger, M. et al. Cell 134, 353–364 (2008).

Gene transfer

A new strategy for zinc-finger nuclease design

Zinc-finger endonucleases can be custom-engineered to induce gene targeting at a user-specified sequence in the genome, but the strategies available to engineer these potentially very useful tools still have limitations. Maeder et al. now present a strategy termed oligomerized pool engineering (OPEN) based on an archive of selected zinc-finger pools and demonstrate its utility by designing nucleases targeting 11 sites in five different genes.

Maeder, M.L. et al. Mol. Cell 31, 294–301 (2008).

Molecular libraries

A library of histone mutants

As a resource for chromatin researchers, Nakanishi et al. present a complete alanine-scanning mutant library of the four core histones in Saccharomyces cerevisiae. They used this library to discover 18 core histone residues that are essential for viability and normal growth as well as to determine regulatory residues required for histone H3 Lys4 methylation.

Nakanishi, S. et al. Nat. Struct. Mol. Biol. 15, 881–888 (2008).

Protein biochemistry

Proximity biotinylation

Fernández-Suárez et al. report a new concept for detecting protein-protein interactions in live cells using an enzyme-substrate pair, exemplified by attaching the enzyme biotin ligase (BirA) to one protein and an acceptor peptide, which is site-specifically biotinylated by BirA, to the interacting protein partner. If the proteins interact, the acceptor peptide will become biotinylated, which can be detected by streptavidin staining.

Fernández-Suárez, M. et al. J. Am. Chem. Soc. 130, 9251–9253 (2008).