In this week's Nature, researchers at the Scripps Research Institute in Jupiter, Fla., and their colleagues report that miR-212, which is "upregulated in the dorsal striatum of rats with a history of extended access to cocaine," decreases responsiveness to cocaine by amplifying the drug's stimulatory effects on CREB signaling. The authors suggest that their study shows that "striatal miR-212 signaling has a key role in determining vulnerability to cocaine addiction, reveal[s] new molecular regulators that control the complex actions of cocaine in the brain reward circuitries, and provide[s] an entirely new direction for the development of anti-addiction therapeutics based on the modulation of noncoding RNAs."
Also in Nature this week, investigators at the University of California, San Francisco, and their colleagues show the "conserved role of intragenic DNA methylation in regulating alternative promoters" using a map of DNA methylation they created, which includes 24.7 of the 28 million CpG sites in the human brain. They found that most of the methylated CpG islands were in intragenic and intergenic regions, "whereas less than three percent of CpG islands in 5' promoters were methylated," the authors write. "These methylation-regulated, alternative transcripts are expressed in a tissue- and cell type-specific manner, and are expressed differentially within a single cell type from distinct brain regions," the team adds.
In Nature Structural & Molecular Biology, a team of researchers report their measurement of genome-wide DNA accessibility in Drosophila "by combining M.SssI methylation footprinting with methylated DNA immunoprecipitation," with which they've determined that "methylase accessibility demarcates differential distribution of active and repressive histone modifications as well as sites of transcription and replication initiation." They also found higher accessibility at chromosomal regions that replicate early at initiation sites. The authors suggest that, taken together, their results show the the organization of replication and differential histone-modification patterns have "measureable effects on the exposure of the DNA template."
And in the most recent issue of Nature Genetics, the Dana-Farber Cancer Institute's Jordi Barretina and several colleagues identify new targets for soft-tissue sarcoma therapy based on subtype-specific genomic alterations — including frequent TP53, NF1, and PIK3CA mutations in the 207 samples, encompassing the seven major subtypes they examined. ShRNA-based knockdown of several genes amplified in de-differentiated liposarcoma effectively decreased cell proliferation, the team writes.