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This Week in Science: Apr 9, 2010

In Science this week, an international research team depicts the genome-wide differences in transcription factor binding among humans that they discovered using ChIP-seq. They mapped the binding sites of RNA polymerase II and nuclear factor κB in 10 lymphoblastoid cell lines; 25 percent of PolII and 7.5 percent of NFκB binding regions varied among individuals. These binding differences, the team writes, were "frequently associated" with SNPs and structural variants; consequently, they were also associated with differences in gene expression, "suggesting functional consequences of binding variation."

Also in Science this week, investigators in the US and the UK report that "heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans." In cataloging individual-to-individual variation, as well as allele-specific variation in chromatic structure and transcription factor binding within individuals of diverse ancestry, the team found that about 10 percent of active chromatin sites were both individual- and allele-specific. Additionally, these sites were shown to be transmitted from parent to offspring, the team writes, suggesting that "they are heritable features of the human genome."

In an advance, online publication of Science, a research team led by investigators at Cancer Research UK discusses the results of their ChIP-seq study that revealed the "evolutionary dynamics of transcription factor binding" in five vertebrate species. The team chose the transcription factors CEBPA and HNF4A to interrogate in the livers of each of the five, and found most binding to be species-specific. "Binding divergence between species can be largely explained by sequence changes to the bound motifs," they write, adding that their results further elucidate the evolution of transcriptional regulation.

Meanwhile, in Science Translational Medicine, researchers suggest that the deregulation of the PI3K pathway in the bronchial epithelial cells of smokers as an "early, measureable, and reversible event in the development of lung cancer and that genomic profiling of these relatively accessible airway cells may example personalized approaches" for therapy. According to the Associated Press, corresponding author Avrum Spira and colleagues are beginning a clinical study of "of up to 800 current and former smokers who need a bronchoscopy anyway to see how well a test based on the research performs."

The Scan

Single-Cell Sequencing Points to Embryo Mosaicism

Mosaicism may affect preimplantation genetic tests for aneuploidy, a single-cell sequencing-based analysis of almost three dozen embryos in PLOS Genetics finds.

Rett Syndrome Mouse Model Study Points to RNA Editing Possibilities

Investigators targeted MECP2 in mutant mouse models of Rett syndrome, showing in PNAS that they could restore its expression and dial down symptoms.

Investigators Find Shared, Distinct Genetic Contributors to Childhood Hodgkin Lymphoma

An association study in JAMA Network Open uncovers risk variants within and beyond the human leukocyte antigen locus.

Transcriptomic, Epigenetic Study Appears to Explain Anti-Viral Effects of TB Vaccine

Researchers report in Science Advances on an interferon signature and long-term shifts in monocyte cell DNA methylation in Bacille Calmette-Guérin-vaccinated infant samples.