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This Week in Nature: Nov 12, 2010

In a paper published online in advance in Nature this week, a research collaboration headed up by investigators at Children's Hospital Boston shows that somatic TET2 mutations, which are common in myelodysplastic syndromes, compromise catalytic activity in the conversion of 5-methylcytosine to 5-hydroxymethylcytosine in DNA. The team found that bone marrow samples from patients with TET2 mutations and mouse hematopoietic precursors subjected to shRNA-mediated depletions of the gene both showed that "disruption of TET2 enzymatic activity favors myeloid tumorigenesis," the authors write.

Also in Nature this week, an international research team describes "a novel pharmacological approach that targets inflammatory gene expression by interfering with the recognition of acetylated histones by the bromodomain and extra terminal domain family of proteins." More specifically, the team's histone mimic — dubbed I-BET — "disrupts chromatin complexes responsible for the expression of key inflammatory genes in activated macrophages, and confers protection against lipopolysaccharide-induced endotoxic shock and bacteria-induced sepsis," the authors write, adding that synthetic compounds such as theirs may be powerful tools in "a new generation of immunomodulatory drugs."

Researchers at the Baylor College of Medicine and their colleagues propose how mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator methyl-CpG-binding protein 2, cause Rett syndrome and cognitive, neurodevelopmental disorders such as "autism, juvenile-onset schizophrenia, and encephalopathy with early lethality." In a mouse model, the Baylor-led team shows that a lack of "Mecp2 from GABA-releasing neurons" and the "loss of MeCP2 from a subset of forebrain GABAergic neurons" recapitulate features of Rett syndrome and autism.

And in Nature Genetics this week, investigators in France describe the "targets and dynamics of promoter DNA methylation during early mouse development." In profiling methylation in an in vivo mouse embryonic lineage, the team "observed a major epigenetic switch during implantation at the transition from the blastocyst to the post-implantation epiblast," during which methylation is "primarily targeted to repress the germline expression program." In the epiblast, DNA methylation is "targeted to promoters of lineage-specific genes such as hematopoietic genes, which are subsequently demethylated during terminal differentiation," the authors write.

The Scan

Billions for Antivirals

The US is putting $3.2 billion toward a program to develop antivirals to treat COVID-19 in its early stages, the Wall Street Journal reports.

NFT of the Web

Tim Berners-Lee, who developed the World Wide Web, is auctioning its original source code as a non-fungible token, Reuters reports.

23andMe on the Nasdaq

23andMe's shares rose more than 20 percent following its merger with a special purpose acquisition company, as GenomeWeb has reported.

Science Papers Present GWAS of Brain Structure, System for Controlled Gene Transfer

In Science this week: genome-wide association study ties variants to white matter stricture in the brain, and more.