Molecular libraries

Histone mutant libraries

It is well appreciated that the functions of core histones are largely controlled by combinatorial post-translational modifications, but individual amino acid residues are also important in regulating DNA-damage response, transcriptional activation and heterochromatin formation. Dai et al. describe a systematic yeast-based library of histone H3 and H4 mutants, which they used to explore the contribution of each individual residue to nucleosome function.

Dai, J. et al. Cell 134, 1066–1078 (2008).

Genomics

Genomic analyses of tumors

To really understand cancer biology it is important to understand all of its genetic and genomic alterations. Several groups have launched large-scale, multidimensional efforts to analyze copy-number variations and gene expression in human glioblastomas and pancreatic cancer. All data of these global genomic analyses are freely accessible.

Jones, S. et al. Science 321, 1801–1806 (2008).

Parsons, D.W. et al. Science 321, 1807–1812 (2008).

The Cancer Genome Atlas Research Network. Nature, published online 4 September 2008.

Chemical biology

Chemical control of proteins in mice

Banaszynski et al. expanded a previously developed method to control protein function in cells. They express a protein of interest as a fusion to an unstable domain. The unstable fusion protein is targeted for degradation, but the presence of a stabilizing ligand protects the fusion protein from degradation, in a dose-dependent manner. By using a viral vector to deliver the fusion protein, they now show they can control protein function in living mice.

Banaszynski, L.A. et al. Nat. Med. 14, 1123–1127 (2008).

Stem cells

iPS cells without viral integration

Reprogramming of somatic cells to yield induced pluripotent stem (iPS) cells has only been achieved so far using technology that requires viral integration into the host cell genome. This poses problems for the safety of the approach, particularly in a clinical setting. Stadtfeld et al. now show that transient expression of Oct4, Sox2, Klf4 and c-Myc from non-integrating adenoviral vectors can reprogram mouse somatic cells to pluripotency.

Stadtfeld, M. et al. Science, published online 25 September 2008.

Protein biochemistry

Evolving streptavidin

The extremely strong interaction between streptavidin and biotin has been exploited for many applications. Levy and Ellington used in vitro compartmentalization–based directed evolution methods to generate streptavidin mutants that bind the biotin analog desthiobiotin with the same affinity as the wild-type enzyme but with a 50-fold slower off rate, which may facilitate new applications. The method should also be applicable for evolving other very high affinity protein-ligand interactions.

Levy, M. & Ellington, A.D. Chem. Biol. 15, 979–989 (2008).