Cell Biology

3D cell culture on paper

Systems for three-dimensional (3D) cell culture exist, but controlling the distribution of oxygen and nutrients remains a challenge. Derda et al. now report a simple approach for constructing paper-supported 3D cell cultures. They added a hydrogel precursor solution containing suspended cells to a small piece of paper and gelled it in place. This allowed them to stack multiple layers of gelled paper to generate a 3D culture system. These stacks can also be readily destacked to examine the cells in the center of the culture.

Derda, R. et al. Proc. Natl. Acad. Sci. USA 106, 18457–18462 (2009).

RNA interference

Predicting targets of microRNA

MicroRNAs regulate gene expression by binding to mRNAs and inhibiting translation. Algorithms for discovering microRNA-mRNA pairs have been developed but are prone to inaccuracies, so Ritchie et al. set out to develop an alternative approach for microRNA target discovery based on comparing the expression levels of microRNAs and mRNAs in mouse and in human, across multiple tissues. They used the conserved microRNA signatures to predict thousands of microRNA targets.

Ritchie, W. et al. PLoS Comput. Biol. 5, e1000513 (2009).

Genomics

Human methylome at base pair resolution

After Arabidopsis thaliana, Homo sapiens is the second species to have its DNA methylome sequenced in its entirety. Lister et al. subjected bisulfite-converted genomic DNA to high-throughput sequencing and mapped all methylated cytosines in the genomes of human embryonic stem cells, where they found 25% of methylcytosine in non-(C+G) context, and in fetal lung fibroblasts, where non-(C+G) methylation had disappeared.

Lister, R. et al. Nature advance online publication (14 October 2009).

Protein biochemistry

Site-specific histone acetylation

Modifications in the cores of histones have important roles in regulating the structure and function of chromatin. Neumann et al. describe an approach to recombinantly generate site-specifically acetylated histones using an evolved aminoacyl-tRNA synthetase and tRNACUA pair that facilitates the incorporation of acetyl-lysine in response to an amber codon. This method allowed the researchers to investigate the mechanistic role of Lys56 acetylation, a highly conserved modification in histone H3, in detail.

Neumann, H. et al. Mol. Cell 36, 153–163 (2009).

Gene regulation

Knocking down microRNA in chick embryos

There is great interest in studying the function of microRNAs in controlling gene expression during embryonic development. McGlinn et al. now describe an approach for knocking down microRNA function in developing chick embryos by using antagomiRs, engineered antisense oligonucleotides, to specifically target Hox genes. The researchers used this method to explore the function of miR-196 in regulating Hox genes central to axial skeletal patterning.

McGlinn, E. et al. Proc. Natl. Acad. Sci. USA 106, 18610–18615 (2009).