In PLoS Biology this week, investigators at St. Jude Children's Research Hospital show that the homeobox gene "Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis." Specifically, Prox1 — expressed in the dentate gyrus during embryonic development and adult neurogenesis — is expressed in intermediate progenitors, and "required for adult neural stem cell self-maintenance in the sub-granular zone," the authors write. They also show that "the ectopic expression of Prox1 induces premature differentiation of neural stem cells."
In a PLoS Computational Biology paper published this week, Meromit Singer at the University of California, Berkeley, and colleagues present MetMap, a statistical method to determine methylation states in populations. MetMap "produces corrected site-specific methylation states from MethylSeq experiments and annotates unmethylated islands across the genome" and "integrates genome sequence information with experimental data, in a statistically sound and cohesive Bayesian network," the authors write. In this way, the tool "infers the extent of methylation at individual CGs and across regions, and serves as a framework for comparative methylation analysis within and among species." The team validated their method with direct bisulfite sequencing experiments.
A PLoS Genetics paper published this week examines the transcriptomes of two heritable cell types and the "circuit governing their differentiation." Brian Tuch at the University of California, San Francisco, and colleagues used strand-specific, massively parallel sequencing of RNA from Candida albicans white and opaque cells. They write that they found "hundreds of novel differentially expressed transcripts." They then compared transcript abundance between the two cell types at the genomic regions bound by Wor1, a regulator of the white-opaque switch. "More than one third of the Wor1-bound differentially-expressed transcripts were previously unannotated, which explains the formerly puzzling presence of Wor1 at these positions along the genome," the authors write, adding that the Wor1 circuit is similar to that of Oct4.
In the same journal, a team of researchers at the University of Minnesota and their colleagues at the Weizmann Institute of Science show that "epigenetically inherited centromere and neocentromere DNA replicates earliest in S-phase." Using a C. albicans model, the team determined genome-wide replication timing and found that "each centromere is associated with a replication origin that is the first to fire on its respective chromosome." Amnon Koren et al. suggest that the "inheritance of centromere position is correlated with a constitutively active origin of replication."