Stem cell plasticity, acetylation of H3K14, and de novo gene activation rely on KAT7.

In the conventional model of transcriptional activation, transcription factors bind to response elements and recruit co-factors, including histone acetyltransferases. Contrary to this model, we show that the histone acetyltransferase KAT7 (HBO1/MYST2) is required genome wide for histone H3 lysine 14 acetylation (H3K14ac). Examining neural stem cells, we find that KAT7 and H3K14ac are present not only at transcribed genes but also at inactive genes, intergenic regions, and in heterochromatin. KAT7 and H3K14ac were not required for the continued transcription of genes that were actively transcribed at the time of loss of KAT7 but indispensable for the activation of repressed genes. The absence of KAT7 abrogates neural stem cell plasticity, diverse differentiation pathways, and cerebral cortex development. Re-expression of KAT7 restored stem cell developmental potential. Overexpression of KAT7 enhanced neuron and oligodendrocyte differentiation. Our data suggest that KAT7 prepares chromatin for transcriptional activation and is a prerequisite for gene activation.

Using long-read sequencing to detect imprinted DNA methylation.

Systematic variation in the methylation of cytosines at CpG sites plays a critical role in early development of humans and other mammals. Of particular interest are regions of differential methylation between parental alleles, as these often dictate monoallelic gene expression, resulting in parent of origin specific control of the embryonic transcriptome and subsequent development, in a phenomenon known as genomic imprinting. Using long-read nanopore sequencing we show that, with an average genomic coverage of ∼10, it is possible to determine both the level of methylation of CpG sites and the haplotype from which each read arises. The long-read property is exploited to characterize, using novel methods, both methylation and haplotype for reads that have reduced basecalling precision compared to Sanger sequencing. We validate the analysis both through comparison of nanopore-derived methylation patterns with those from Reduced Representation Bisulfite Sequencing data and through comparison with previously reported data. Our analysis successfully identifies known imprinting control regions (ICRs) as well as some novel differentially methylated regions which, due to their proximity to hitherto unknown monoallelically expressed genes, may represent new ICRs.

The future of optometric practice? The results of a survey of optometrists and optometry students.

BACKGROUND: There is an apparent increase in the number of private optometry practices that are closing due to a lack of interested buyers. We examined some of the factors that influence the market for optometry practices in a survey of practicing optometrists and third- and fourth-year optometry students. METHODS: Optometrists in six states, and students at four schools and colleges of optometry, completed a mailed or faxed survey regarding attitudes toward optometric practice, including fair/reasonable compensation for a new optometrist, the value of optometric practices, and preferred mode of practice on graduation. RESULTS: Doctors and students differed significantly in the amount of money they reported as fair/reasonable compensation for a recently graduated optometrist joining a practice. Comparing students to doctors in specific categories of compensation, students chose a higher fair/reasonable compensation compared to doctors. Students were more likely than doctors to choose >$70,000 as fair/reasonable compensation, while doctors were more likely than students to choose $40,000 to $69,000. Doctors tended to overvalue their practices for the purpose of selling the practice when using percentage of gross income as a valuation method. Students' choices for mode of practice changed dramatically from their ideal when taking their current financial situation into consideration. Students were more likely to choose corporate practice as their preferred practice mode when considering their current financial situation than when not restricted. CONCLUSIONS: There are many factors that affect the value and marketability of an optometric practice. In order to sell a practice, the owner must consider the effects of the needs and desires of recently graduated optometrists.